mtDNA突变与乳腺癌相关性研究
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摘要
[目的]
研究线粒体DNA (mitochondrial DNA, mtDNA)控制区(control region)中体细胞突变(somatic mutation)与乳腺肿瘤发生发展的相关性。
[方法]
对来自云南昆明的28例恶性乳腺肿瘤患者的肿瘤组织及外周血和25例良性乳腺肿瘤患者的肿瘤组织及外周血mtDNA的控制区中的第一高变区(HVS-Ⅰ)及第二高变区(HVS-Ⅱ)区段进行PCR扩增及DNA测序,以修订过的剑桥标准序列Prevised Cambridge reference sequence; rCRS)为标准比对并记录突变位点,且利用系统发育的分析方法构,判断它们的单倍型类群(参照部分编码区信息)。比较其突变分布差异,揭示可能存在的肿瘤组织特有体细胞突变。
[结果]
28例恶性乳腺肿瘤患者mtDNA的控制区HVS-Ⅰ、HVS-Ⅱ共发现8个体细胞突变,突变频率为28.6%,包括309+CC(样本BC6)、309+C(样本BC20、样本BC26)、279Y(样本BC16)、297R(样本BC16)、214R(样本BC21)、190Y(样本BC61)和204Y(样本BC64)；而25例良性乳腺肿瘤患者中则发现2个体细胞突变,突变频率为15.4%,包括16292Y(样本BCA10)和309+CC(样本BCA12)。统计学分析发现P=0.03,表明恶性乳腺肿瘤与良性乳腺肿瘤mtDNA控制区的体细胞突变存在显著差异。本研究还发现的10个体细胞突变中有4个(40%)是D310区polyC的多态。
对28例乳腺癌患者体细胞突变与肿瘤免疫组化雌孕激素受体、HER-2基因表达情况及腋窝淋巴结转移情况等进行分析,发现体细胞突变与雌激素受体阳性表达有相关性。
[结论]
恶性乳腺肿瘤患者mtDNA控制区的体细胞突变频率明显高于良性乳腺肿瘤患者,提示mtDNA的体细胞突变可能确实与肿瘤的发生、癌变相关；mtDNA控制区的体细胞突变可能在乳腺肿瘤的发生发展中起重要作用；在乳腺肿瘤中D310区是突变热点区域,可能与乳腺肿瘤的发生发展有着一定的联系,与以往的研究结果相符合。
另外,从1ntDNA单倍型类群的角度出发,病人组和正常对照组之间的对比分析没有发现与乳腺肿瘤存在显著相关的mtDNA单倍型类群,结合其它研究结果报道,提示我们母系遗传背景在乳腺肿瘤患者中的作用可能很小。
恶性乳腺肿瘤患者mtDNA控制区的体细胞突变与雌激素受体阳性表达有相关性,需增加样本量,进一步深入研究其意义。
[目的]
基于线粒体DNA (mtDNA)的全基因组信息研究mtDNA体细胞突变与乳腺良性疾病发生的相关性。
[方法]
对来自云南昆明市第一人民医院乳腺科诊治的28例良性乳腺疾病患者的病变组织mtDNA全基因组序列进行聚合酶链反应(PCR)扩增及DNA测序；以修订过的剑桥标准序列为标准比对并记录突变位点,参照东亚线粒体DNA系统发育树(phylogenetic tree)来确定其系统发育地位；通过单倍型类群(haplogroup)划分并与前期发表的mtDNA全基因组数据比较,识别出个体(或组织)特有的变异(即私有突变)及其与已报道mtDNA序列共享有的突变位点(即单倍型类群特征变异；haplogroup-diagnostic variation);通过对病人mtDNA的单倍型类群识别并将其构建系统发育关系树；通过与同一病患个体外周血mtDNA变异模式比较,揭示可能存在的乳腺良性病变组织特有的体细胞突变。
[结果]
研究获得了乳腺良性疾病患者病变组织mtDNA全基因组的突变图谱,并构建了系统发育关系树；28例良性乳腺疾病患者的病变组织的mtDNA全基因组信息,发现了7个体细胞变异,其中,BCA10病人16292位置存在体细胞突变,16292位于第一高变区,另外6个体细胞突变均位于mtDNA编码区中,除了1个突变(5567)位于tRNA之外,剩余5个突变均位于蛋白编码基因上,且其中4个均为非同义突变(即均引起了氨基酸变化),结果揭示,28例患者的mtDNA分别归属为单倍型类群M7b、M7c2、C、D4b2b、D4i、D4k、D5a2、D5b、G1、R9b、F1、B5b、B4c2a、 B4d、R11、R22及N9a。
[结论]
本课题对28例良性乳腺疾病患者病变组织的mtDNA全基因组信息进行了研究,结果发现7个体细胞突变,1个位于控制区而另外6个均位于编码区,且存在于：mtDNA编码区区段中的体细胞突变大部分(4/6)均为非同义突变,会引发编码氨基酸的变化,提示这些mtDNA突变在乳腺良性疾病的发生、发展中可能存在潜在的作用。
过去的相关研究仅仅基于mtDNA控制区片段的研究,所揭示的信息显然非常有限,而本课题的研究是基于全基因组信息对mtDNA在乳腺疾病发生发展过程中发挥的作用有较系统而深入的了解。可引发氨基酸变化的肿瘤特异体细胞的突变,在疾病发生发展过程中可能起着重要作用,这些mtDNA突变也可能为将来乳腺肿瘤的临床诊断提供潜在有价值的遗传标记。
伴有乳腺癌高危因素的乳腺良性疾病患者,mtDNA的体细胞突变高于没有乳腺癌高危因素的乳腺良性疾病患者,为乳腺癌的患病风险,提供一项新的依据。但因研究样本量太少,还有待进一步研究。
[Objective]
To investigate the somatic mutations in control region of mitochondrial DNA (mtDNA) in patients with breast tumor in Yunnan Province.
[Methods]
The genomic DNA of tumor tissue and peripheral blood in28breast cancer patients and25benign breast tumor patients were extracted. mtDNA D-loop region (including its HVR1and HVR2) of each sample was amplified and sequenced with two pairs of primers. The somatic mutations were identified by comparing the mutation spectra between tumor tissue and peripheral blood.
[Results]
Totally,8somatic mutations were found in28breast cancer patients, including309+CC (sample BC6),309+C (sample BC20, sample BC26),279Y (sample BC16),297R (sample BC16),214R (sample BC21),190Y (sample BC61) and204Y (sample BC64);2somatic mutations in25benign breast tumor patients were found, including16292Y (sample BCA10) and309+CC (sample BCA12). Further analysis revealed that somatic mutations occurred more frequently in breast cancer patients (28.6%) than in benign breast tumor (15.4%)(P=0.03).
We analyze the somatic mutations,immunhistochemistry of tumor's estrogen receptor,gene of HER-2and the lymph node metastasis of bilateral axillary in28breast cancer patients.Finally,we found that there were some relationship between somatic mutations and estrogen receptor expression.
[Conclusion]
Our data suggest that somatic mutations in mtDNA D-loop HVR1and HVR2may play some role in the pathogenesis of breast cancer, at least in the patients form Yunnan Province.
Others,we didn't found the mtDNA haplogroup had significant correlation of breast tumor,combined with other studies,we can conclude that maternal genetic effect is small in breast tumor.
In view of the relationship between somatic mutations and estrogen receptor expression,we can concluded if increase the number of sample,it can further study the relationship between somatic mutations and breast caner by estrogen receptor.
[Objective]
To investigate on the potential role of mtDNA somatic mutations in benign breast disease based on the entire mtDNA genome study,found out the relationship between benign breast disease and breast cancer.
[Methods]
The genomic DNA of tumorous tissue and peripheral blood in28benign breast disease patients were extracted respectively. The mtDNA whole genome was amplified into two overlapping segments, which were then sequenced respectively by using inner primers. Variants of each mtDNA genome were recorded according to the revised Cambridge reference sequence. The private variation (of each tumor tissue) was pinpointed by means of phylogenetic tree reconstruction, which was then screened in the mtDNA from the matched peripheral blood, with especial attention to verify whether the distilled variation is private to the patient or in fact specific to the tumor issue (viz. somatic variation).
[Results]
Based on the obtained mutation spectrum of mtDNA genomes, the phylogenetic tree was then reconstructed to identify their haplogroup status.Our results revealed7somatic mutations among the tissues of the28patients, among which1mutation locates in the control region whereas the rest6lie in the coding region. Further analyses revealed that, out of these6coding-region mutations,4are non-synonymous and will introduce change of AA.
[Conclusion]
Based on the extensively study on the mtDNA genomes from the issues of28benign breast disease patients, our current report observed a number of7somatic mutations. With the exception of16292that locates in the control region, the rest6are distributed in coding region, and most of which (4/6) are non-synonymous substitutions and will lead to the change of amino acid, indicating that these mtDNA mutations likely have some functional potential in tumorigenesis. Most significantly, our study further suggests the particular necessity of taking the entire genome of mtDNA into consideration during the study of tumorigenesis.
Our topic based on genome-wide information's effect of mtDNA in breast disease,we could get the result that mtDNA matation may play an important role in the development of breast disease.Also,these mtDNA matation may could provide valuable genetic markers in clinical diagnosis of breast disease.
The benign breast disease patient who accompanied by risk factors of breast cancer,their mtDNA somatic mutations were more than the perosn who didn't companied.In this regard,we look forward to further research.
研究线粒体DNA (mitochondrial DNA, mtDNA)控制区(control region)中体细胞突变(somatic mutation)与乳腺肿瘤发生发展的相关性。
[方法]
对来自云南昆明的28例恶性乳腺肿瘤患者的肿瘤组织及外周血和25例良性乳腺肿瘤患者的肿瘤组织及外周血mtDNA的控制区中的第一高变区(HVS-Ⅰ)及第二高变区(HVS-Ⅱ)区段进行PCR扩增及DNA测序,以修订过的剑桥标准序列Prevised Cambridge reference sequence; rCRS)为标准比对并记录突变位点,且利用系统发育的分析方法构,判断它们的单倍型类群(参照部分编码区信息)。比较其突变分布差异,揭示可能存在的肿瘤组织特有体细胞突变。
[结果]
28例恶性乳腺肿瘤患者mtDNA的控制区HVS-Ⅰ、HVS-Ⅱ共发现8个体细胞突变,突变频率为28.6%,包括309+CC(样本BC6)、309+C(样本BC20、样本BC26)、279Y(样本BC16)、297R(样本BC16)、214R(样本BC21)、190Y(样本BC61)和204Y(样本BC64)；而25例良性乳腺肿瘤患者中则发现2个体细胞突变,突变频率为15.4%,包括16292Y(样本BCA10)和309+CC(样本BCA12)。统计学分析发现P=0.03,表明恶性乳腺肿瘤与良性乳腺肿瘤mtDNA控制区的体细胞突变存在显著差异。本研究还发现的10个体细胞突变中有4个(40%)是D310区polyC的多态。
对28例乳腺癌患者体细胞突变与肿瘤免疫组化雌孕激素受体、HER-2基因表达情况及腋窝淋巴结转移情况等进行分析,发现体细胞突变与雌激素受体阳性表达有相关性。
[结论]
恶性乳腺肿瘤患者mtDNA控制区的体细胞突变频率明显高于良性乳腺肿瘤患者,提示mtDNA的体细胞突变可能确实与肿瘤的发生、癌变相关；mtDNA控制区的体细胞突变可能在乳腺肿瘤的发生发展中起重要作用；在乳腺肿瘤中D310区是突变热点区域,可能与乳腺肿瘤的发生发展有着一定的联系,与以往的研究结果相符合。
另外,从1ntDNA单倍型类群的角度出发,病人组和正常对照组之间的对比分析没有发现与乳腺肿瘤存在显著相关的mtDNA单倍型类群,结合其它研究结果报道,提示我们母系遗传背景在乳腺肿瘤患者中的作用可能很小。
恶性乳腺肿瘤患者mtDNA控制区的体细胞突变与雌激素受体阳性表达有相关性,需增加样本量,进一步深入研究其意义。
[目的]
基于线粒体DNA (mtDNA)的全基因组信息研究mtDNA体细胞突变与乳腺良性疾病发生的相关性。
[方法]
对来自云南昆明市第一人民医院乳腺科诊治的28例良性乳腺疾病患者的病变组织mtDNA全基因组序列进行聚合酶链反应(PCR)扩增及DNA测序；以修订过的剑桥标准序列为标准比对并记录突变位点,参照东亚线粒体DNA系统发育树(phylogenetic tree)来确定其系统发育地位；通过单倍型类群(haplogroup)划分并与前期发表的mtDNA全基因组数据比较,识别出个体(或组织)特有的变异(即私有突变)及其与已报道mtDNA序列共享有的突变位点(即单倍型类群特征变异；haplogroup-diagnostic variation);通过对病人mtDNA的单倍型类群识别并将其构建系统发育关系树；通过与同一病患个体外周血mtDNA变异模式比较,揭示可能存在的乳腺良性病变组织特有的体细胞突变。
[结果]
研究获得了乳腺良性疾病患者病变组织mtDNA全基因组的突变图谱,并构建了系统发育关系树；28例良性乳腺疾病患者的病变组织的mtDNA全基因组信息,发现了7个体细胞变异,其中,BCA10病人16292位置存在体细胞突变,16292位于第一高变区,另外6个体细胞突变均位于mtDNA编码区中,除了1个突变(5567)位于tRNA之外,剩余5个突变均位于蛋白编码基因上,且其中4个均为非同义突变(即均引起了氨基酸变化),结果揭示,28例患者的mtDNA分别归属为单倍型类群M7b、M7c2、C、D4b2b、D4i、D4k、D5a2、D5b、G1、R9b、F1、B5b、B4c2a、 B4d、R11、R22及N9a。
[结论]
本课题对28例良性乳腺疾病患者病变组织的mtDNA全基因组信息进行了研究,结果发现7个体细胞突变,1个位于控制区而另外6个均位于编码区,且存在于：mtDNA编码区区段中的体细胞突变大部分(4/6)均为非同义突变,会引发编码氨基酸的变化,提示这些mtDNA突变在乳腺良性疾病的发生、发展中可能存在潜在的作用。
过去的相关研究仅仅基于mtDNA控制区片段的研究,所揭示的信息显然非常有限,而本课题的研究是基于全基因组信息对mtDNA在乳腺疾病发生发展过程中发挥的作用有较系统而深入的了解。可引发氨基酸变化的肿瘤特异体细胞的突变,在疾病发生发展过程中可能起着重要作用,这些mtDNA突变也可能为将来乳腺肿瘤的临床诊断提供潜在有价值的遗传标记。
伴有乳腺癌高危因素的乳腺良性疾病患者,mtDNA的体细胞突变高于没有乳腺癌高危因素的乳腺良性疾病患者,为乳腺癌的患病风险,提供一项新的依据。但因研究样本量太少,还有待进一步研究。
[Objective]
To investigate the somatic mutations in control region of mitochondrial DNA (mtDNA) in patients with breast tumor in Yunnan Province.
[Methods]
The genomic DNA of tumor tissue and peripheral blood in28breast cancer patients and25benign breast tumor patients were extracted. mtDNA D-loop region (including its HVR1and HVR2) of each sample was amplified and sequenced with two pairs of primers. The somatic mutations were identified by comparing the mutation spectra between tumor tissue and peripheral blood.
[Results]
Totally,8somatic mutations were found in28breast cancer patients, including309+CC (sample BC6),309+C (sample BC20, sample BC26),279Y (sample BC16),297R (sample BC16),214R (sample BC21),190Y (sample BC61) and204Y (sample BC64);2somatic mutations in25benign breast tumor patients were found, including16292Y (sample BCA10) and309+CC (sample BCA12). Further analysis revealed that somatic mutations occurred more frequently in breast cancer patients (28.6%) than in benign breast tumor (15.4%)(P=0.03).
We analyze the somatic mutations,immunhistochemistry of tumor's estrogen receptor,gene of HER-2and the lymph node metastasis of bilateral axillary in28breast cancer patients.Finally,we found that there were some relationship between somatic mutations and estrogen receptor expression.
[Conclusion]
Our data suggest that somatic mutations in mtDNA D-loop HVR1and HVR2may play some role in the pathogenesis of breast cancer, at least in the patients form Yunnan Province.
Others,we didn't found the mtDNA haplogroup had significant correlation of breast tumor,combined with other studies,we can conclude that maternal genetic effect is small in breast tumor.
In view of the relationship between somatic mutations and estrogen receptor expression,we can concluded if increase the number of sample,it can further study the relationship between somatic mutations and breast caner by estrogen receptor.
[Objective]
To investigate on the potential role of mtDNA somatic mutations in benign breast disease based on the entire mtDNA genome study,found out the relationship between benign breast disease and breast cancer.
[Methods]
The genomic DNA of tumorous tissue and peripheral blood in28benign breast disease patients were extracted respectively. The mtDNA whole genome was amplified into two overlapping segments, which were then sequenced respectively by using inner primers. Variants of each mtDNA genome were recorded according to the revised Cambridge reference sequence. The private variation (of each tumor tissue) was pinpointed by means of phylogenetic tree reconstruction, which was then screened in the mtDNA from the matched peripheral blood, with especial attention to verify whether the distilled variation is private to the patient or in fact specific to the tumor issue (viz. somatic variation).
[Results]
Based on the obtained mutation spectrum of mtDNA genomes, the phylogenetic tree was then reconstructed to identify their haplogroup status.Our results revealed7somatic mutations among the tissues of the28patients, among which1mutation locates in the control region whereas the rest6lie in the coding region. Further analyses revealed that, out of these6coding-region mutations,4are non-synonymous and will introduce change of AA.
[Conclusion]
Based on the extensively study on the mtDNA genomes from the issues of28benign breast disease patients, our current report observed a number of7somatic mutations. With the exception of16292that locates in the control region, the rest6are distributed in coding region, and most of which (4/6) are non-synonymous substitutions and will lead to the change of amino acid, indicating that these mtDNA mutations likely have some functional potential in tumorigenesis. Most significantly, our study further suggests the particular necessity of taking the entire genome of mtDNA into consideration during the study of tumorigenesis.
Our topic based on genome-wide information's effect of mtDNA in breast disease,we could get the result that mtDNA matation may play an important role in the development of breast disease.Also,these mtDNA matation may could provide valuable genetic markers in clinical diagnosis of breast disease.
The benign breast disease patient who accompanied by risk factors of breast cancer,their mtDNA somatic mutations were more than the perosn who didn't companied.In this regard,we look forward to further research.
引文
1.雷秋模.现代诊断与治疗.21世纪乳腺癌研究的方向及展望.2006,3月,17(2)：65-67
2. Andrews, R.M., I. Kubacka, P.F. Chinnery, R.N. Lightowlers, D.M. Turnbull, and N. Howell. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet,1999,23(2):147.
3. Anderson, S., A.T. Bankier, B.G. Barrell, M.H. de Bruijn, A.R. Coulson, J. Drouin, I.C. Eperon, D.P. Nierlich, B.A. Roe, F. Sanger, P.H. Schreier, A.J. Smith, R. Staden, and I.G. Young. Sequence and organization of the human mitochondrial genome. Nature, 1981,290(5806):457-65.
4. Fliss MS, Usadel H, Caballero OL, et al. Facile Detection of Mitochondrial DNA Mutations in Tumors and Bodily Fluids. Science,2000,287(5460):2017-2019.
5.Chen J Z, Gokdem N, Green G F, et al. SilIlultaneondrial generation of multiple mitochondrial DNA mutations in humam prostate tumors suggests mitochondrial hyper-mutagenesis. Caminogenesis,2003,24(9):1481-1487.
6.Kiches E, Mawrin C, Schneider Stock R et al. Mitochondrial DNA as a clonal tumor marker:glimatosis cerebri. J Neurooncol,2003,61(1):1-5.
7. Bianchi NO, Bianchi MS, Richard SM. Mitochondrial genome instability in human cancers. Mutat Res,2001,488:9-23.
8.Richard SM, Bailliet G, Paez GL, et al. Nuclear and mitochondrial genome instability in human breast cancer. Cancer Res,2000,60:4231-4237.
9.Suzuki M, Toyooka S, Miyajima K, et al. Alterations in the mitochondrial displacement loop in lung cancers. Clin Cancer Res,2003,9:5636-5641.
10. Warburg O. On the Origin of Cancer Cells. Science,1956,123(3191):309-314
11. Lievre A, Chapusot C, Bouvier AM, et al. Clinical value of mitochondrial mutations in colorectal cancer. J Clin Oncol,2005,23:3517-3525.
12. Tan DJ, Bai RK, Wong LJ. Comprehensive scanning of somatic mitochondrial DNA mutations in breast cancer. Cancer Res 2002,62:972-976.
13. Polyak K, Li Y, Zhu H, et al. Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet,1998,20(3):291-293.
14. Liu VW, Shi HH, Cheung AN, Chiu PM, Leung TW, Nagley P, Wong LC, Ngan HY. High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas. Cancer Res 2001,61:5998-6001.
15. liss MS, Usadel H, Caballero OL, et al. Facile Detection of Mitochondrial DNA Mutations in Tumors and Bodily Fluids. Science,2000,287(5460):2017-2019.
16. Wu CW, Yin PH, Hung WY, Li AF, Li SH, Chi CW, Wei YH, Lee HC. Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosomes Cancer 2005,44:19-28.
17. Nishikawa M, Nishiguchi S, Shiomi S, Tamori A, Koh N, Takeda T, Kubo S, Hirohashi K, Kinoshita H, Sato E, Inoue M. Somatic mutation of mitochondrial DNA in cancerous and noncancerous liver tissue in individuals with hepatocellular carcinoma. Cancer Res 2001,61:1843-1845.
18. Jeronimo C, Nomoto S, Caballero OL, Usadel H, Henrique R, Varzim G, Oliveira J, Lopes C, Fliss MS, Sidransky D. Mitochondrial mutations in early stage prostate cancer and bodily fluids. Oncogene 2001,20:5195-5198.
19. Petros JA, Baumann AK, Ruiz-Pesini E, et al. mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci USA,2005,102(3):719-724.
20. Abu-Amero KK, Alzahrani AS, Zou M, Shi Y. High frequency of somatic mitochondrial DNA mutations in human thyroid carcinomas and complex I respiratory defect in thyroid cancer cell lines. Oncogene 2005,24:1455-1460.
21. Hibi K, Nakayama H, Yamazaki T, et al. Detection of mitochondrial DNA alterations in primary tumors and corresponding serum of colorectal cancer patients. Int J Cancer, 2001,94(3):429-431.
22. Sanchez-Cespedes M, Parrella P, Nomoto S, Cohen D, Xiao Y, Esteller M, Jeronimo C, Jordan RC, Nicol T, Koch WM, Schoenberg M, Mazzarelli P, et al. Identification of a mononucleotide repeat as a major target for mitochondrial DNA alterations in human tumors. Cancer Res 2001,61:7015-7019.
23. Carew JS, Huang P. Mitochondrial defects in cancer. Mol Cancer 2002,1:9.
24. Chatterjee A, Mambo E, Sidransky D. Mitochondrial DNA mutations in human cancer. Oncogene 2006,25:4663-4674.
25. Brandon M, Baldi P, Wallace DC. Mitochondrial mutations in cancer. Oncogene 2006, 25:4647-4662.
26. Canter JA, Kallianpur AR, Parl FF, Millikan RC. Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res 2005,65:8028-8033.
27. Liu VW, Wang Y, Yang HJ, Tsang PC, Ng TY, Wong LC, Nagley P, Ngan HY. Mitochondrial DNA variant 16189T>C is associated with susceptibility to endometrial cancer. Hum Mutat 2003,22:173-174.
28. Jakupciak JP, Dakubo GD, Maragh S, Parr RL. Analysis of potential cancer biomarkers in mitochondrial DNA. Curr Opin Mol Ther 2006,8:500-506.
29. Nomoto S, Yamashita K, Koshikawa K, Nakao A, Sidransky D. Mitochondrial D-loop mutations as clonal markers in multicentric hepatocellular carcinoma and plasma. Clin Cancer Res 2002,8:481-487.
30. Beckman KB, and Ames BN. Oxidative decay of DNA. J Biol Chem,1997, 272:19633-19636.
31. Stoneking M. Hypervariable sites in the mtDNA control region are mutational hotspots. Am J Hum Genet,2000,67:1029-1032.
32. Vanecek T, Vorel F, and Sip M. Mitochondrial DNA D-loop hypervariable regions: Czech population data. Int J Legal Med,2004,118:14-18.
33.Zhu w, Qin w, Bradley P'Wessel A, Puckett CL, Sauter ER. M itochondrial DNA mutations in breast cancer tissue and in matched nipple aspirate fluid. Carcinogenesis, 2005,26(1):145-152.
34. Holt IJ, Harding AE, and Morgan-Hughes JA.1988. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331:717-719.
35. Nomoto S,et al. Mitochondrial D-Loop Mutation As Clonal Markers in Multicentric hepatocellular Carcinoma and Plasma J. Clin Cancer Res,2002.8(2):481-487.
36. Wang CY, Wang HW, Yao YG, et al. Somatic mutations of mitochondrial genome in early stage breast cancer. Int J Cancer,2007,121:1253-1256.
37. Yao YG, Kong QP, Bandelt HJ, et al. Phylogeographic differentiation of mitochondrial DNA in Han Chinese. Am J Hum Genet,2002,70:635-651.
38.蒋学祥,王霄英.正确发挥影像学在乳腺癌诊治中的作用.中华放射学杂志,2010,44(5).453.
39.中华人民共和国卫生部.第三次全国死因调查主要情况.中国肿瘤,2008,17(5)：344-345.
40.沈镇宇,邵志敏.现代乳腺肿瘤学进展.上海,上海科学技术文献出版社.2002.3-5.
41.Jeong H C, Kim J A, ImHH, et al. Mitochondrial DNA sequence variation of the swallow tail, butterfly, papilio xuthus。and the cabbage butterfly, pieris rapae J. Biochem Genet,2009,29. [E pub ahead of print].
42.Rojas M,Gonzalez I.Fajardo C,et al. Polymerase chain reaction- restriction fragment length polymorp hismau thentication of raw meats from game birds[J].J AoAC Int,2008,91:1416-1422.
43. Sehinogl P,Muller M,Steinborn R.Quantification of the 4977-bp deletion in human mitochondrial DNA usingreal-time PCR[J]. Forensic Sci Int,2001,122:197-199.
44. Paez G,Richard S, Bianchi MS, et al. Loss of heterozygosity (LOH) in 15q26.2 in breast cancer. Mutat Res,2001,484:103-106.
45.谭端军,刘玲玲,徐斌等.中国汉族人与美国高加索人乳腺癌患者线粒体基因组突变的比较.中国临床康复,2005,9：114-116.
46.Wang Y, Liu VW, Tsang PC, et al. Microsatellite instability in mitochondrial genome of common female cancers. Int J Gynecol Cancer,2006,16(Suppl 1):259-266.
47.Cavelier L, Jazin E, Jalonen P, and Gyllensten U.2000. MtDNA substitution rate andsegregation of heteroplasmy in coding and noncoding regions. Hum Genet107:45-50.
48. Wallace DC.1994. Mitochondrial DNA sequence variation in human evolution anddisease. Proc Natl Acad Sci U S A 91:8739-8746.
49.Croteau DL, and Bohr VA.1997. Repair of oxidative damage to nuclear andmitochondrial DNA in mammalian cells. J Biol Chem 272:25409-25412.
50.Yao YG, Kong QP, Wang CY, et al. Different matrilineal contributions to genetic structure of ethnic groups in the silk road region in China. Mol Biol Evol,2004, 21:2265-2280.
51.Kong QP, Yao Y, Sun C, et al. Phylogeny of east Asian mitochondrial DNA lineages inferred from complete sequences. Am J Hum Genet,2003,73:671-676.
52.Sun C, Kong QP, Palanichamy MG, et al. The dazzling array of basal branches in the mtDNA macrohaplogroup M from India as inferred from complete genomes. Mol Biol Evol,2006,23:683-690.
53. Penta JS,Johnson FM.Wachsman JT.et al.Mitochondfial DNA in human malignancy.Murat Res,2001,488:119-133.
54.DiMauto S.Schon EA.Mitochondfial DNA mutations in human disease.Am J Med Genet.2001.106:18-26.
55. Poetsch M,Petersmann A,Lignitz E,et al.Relationship between mitochondfial DNA instability,mitochondrial DNA large deletions,and nuclear microsatellite instability in head and neck sqnamous cell carcinomas. Diagn Mel Patllel,2004,13:26-32.
56. Hiyama T,Tanaka S.Shima H.et al.Somatic mutation in mitochondrial DNA and nuclear mien satellite instability in gastric cancer.Oncol Rep.2003.10:1837-1841.
57. Lutz S, Weisser HJ, Heizmann J, and Pollak S.1998. Location and frequency ofpolymorphic positions in the mtDNA control region of individuals fromGermany. Int J Legal Med 111:67-77.
58Jones JB, Song JJ, Hempen PM, Parmigiani G, Hruban RH, and Kern SE. 2001.Detection of mitochondrial DNA mutations in pancreatic cancer offers a"mass"-ive advantage over detection of nuclear DNA mutations. Cancer Res61:1299-1304.
59.Chinnery PF,Samuels DC,Elson J, and Turnbull DM.2002. Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease:is there a common mechanism? Lancet 360:1323-1325.
60.Zhu W,Qin w,Sauter ER.Large-scale mitochondrial DNA deletion mu tations and nuclear genome instability in human breast cancer. Cancer Detect Prev, 2004.28:119.126.
61.Lee HC,Yin PH, Lin JC,et al. Mitochondrial genome instability and mtDNA depletion in human cancers. Ann N Y Acad Sci,2005,1042:109-122.
62.Zhao YB,Yang HY,Zhang XW,et al. Mutation in D-loop region of mitochondrial DNA in gastric cancer and its significance. Work J Castroenterol,2005,11:3304-3306.
63.Rosson D, Keshgegian AA. Frequent mutations in the mitochondrial control region DNA in breast tissue. Cancer Lett,2004,215:89-94.
64.Liane Fendt, Bettina Zimmermann, Martin Daniaux, et al. Sequencing strategy for the whole mitochondrial genome resulting in high quality sequences. BMC Genomics, 2009,10:139.
65.Coller,H.A,K. Khrapko,N.D. Bodyak, E. Nekhaeva, P. Herrero-Jimenez, and W.G. Thilly. High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection. Nat Genet,2001,28(2):147-50.
66.Poetsch M,Petersmann A, Lignitz E,et al.Relationship between mitochondfial DNA instability,mitochondrial DNA large deletions, and nuclear microsatellite instability in head and neck sqnamous cell carcinomas. Diagn Mel Patllel,2004,13:26-32.
67. Hiyama T,Tanaka S.Shima H.et al.Somatic mutation in mitochondrial DNA and nuclear mien)satellite instability in gastric cancer.Oncol Rep2003.10:1837-1841.
68. Perou CM, Sodie T, Eisin MB, et a. Mdecular portraits of human breast tumours[J]. Nature,2000,406(6797):747-752.
69. Nielsen TO,-lsu FD,ensen K,et and clinical characterization of the basal-like subtype Of invasive breast carcinoma[J.]Clin Cancer Res,2004,10(6):5367-5374.
1.陈丽芹,王徐东,张子和等.乳腺疾病的相关因素及防治措施.中国综合临床,(6)2007,23：563.
2.Kronowitz SJ.Robb CL.Breaat reconstruction with p06tmaatectomy radiation therapy: onuuent issues[J]. Plast Reconstr Surg,2004,114(4):950-960.
3.AJchazalak SK, Suuy L, Fallowfield L,et al.The Psychological im. pact Of immediate rather than delayed breconstmction[J].Eur J Surg Oncol,2000,26(1):17-19.
4.李云英.乳腺纤维腺瘤癌变.中国肿瘤临床,1994,21：760.
5.吴祥德,董守义.乳腺疾病诊治.人民卫生出版社,2009：166-168.
6.龚畅,苏逢锡.良性乳腺病的概念转变[J].国外医学外科分册,2004,31：145-148.
7.Bodian CA,Perzin KH,Lattes R,et al.Prognostic significance of benign proliferative breast disease,Cancer,2005,71:3896-3907.
8.Marshall LM,Hunter DJ,ConnollyJL,et al.Risk of breast cancer associated with atypical hyperplasia of lobular and ductaltypes.Cancer Epidemiol Biomarkers Prev, 1997,6:297-301.
9.Dupont WD,Page DL.Risk factors for breast cancer in women with proliferative breast disease.N Engl J Med,2007,312:146-151.
10.Page KL,Dupont WD,Rogers LW,et al,Atypical thperplastic lesions of the female breast:a long-term follow-uo study.Cancer,2006,55:2698-2708.
11.Kodlin D,Winger EE,Morgenstem NL,et al.Chronic mastopathy and breast cancer:a follow-up study.Cancer,1997,39:2603-2607.
12.Carter CL,Corle DK,Micozzi MS,et al.A prospective study of the development of breast cancer in 16692 women with benign breast disease.Am I Epidemiol,1988, 128:467-477.
13.Tacassoli FA,Norris HJ.A comparison of the results of longterm follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast.Cancer,1990, 65:518-529.
14.Palli D,Rosselli del Turco M,simoncini R,et al.Benign breast disease and breast cancer:a case-control study in a cohort in Italy.Int J Cancer,1991,47:703-706.
15.Lindon SJ,Connolly JL,Schnitt SJ,et al.A prospective study of benign breast disease and the risk of breast cancer.JAMA,2006,267:941-944.
16.Krieger N,.Hiatt RA.Risk of breast cancer after benign bresat diseases:variation by histologic type,degree of atypia,age at biopsy,and length of follow-up. Am J Epidemiol, 2007,135:619-631.
17.Parrella P,Liao Y,Hiss M,et al.Detection of mitochondrial DNA mutations in primary breast CanCer and fine-needle aspirates.Cancer Res 2001,61(20):7623-6.
18.周云丽,牛瑞芳,史玉荣等.乳腺癌线粒体DNA拷贝数改变的研究及意义.中华肿瘤防治杂志2006.13(14)：1082-84.
19.Bandelt HJ,Lahermo P,Richards M,and Macaulay V.2001.Detecting errors in mtDNA data by phylogenetic analysis. Int J Legal Med 115:64-69.
20.Bandelt HJ, Achilli A, Kong QP, Salas A, Lutz-Bonengel S, Sun C, Zhang YP, TorroniA, and Yao YG.2005a. Low "penetrance" of phylogenetic knowledge in mitochondrial disease studies. Biochem Biophys Res Commun 333:122-130.
21.Bandelt HJ, Kong QP, Parson W, and Salas A.2005b. More evidence for non-maternalinheritance of mitochondrial DNA J Med Genet 42:957-960.
22.Ingman M, Kaessmann H, Paabo S, and Gyllensten U.2000. Mitochondrial genomevariation and the origin of modern humans. Nature 408:708-713.
23.Maca-Meyer N,Gonzalez AM,Larruga JM,Flores C,and Cabrera VM.2001. Major genomic mitochondrial lineages delineate early human expansions. BMC Genet 2:13.
24.Kivisild T, Tolk HV, Parik J, Wang Y, Papiha SS, Bandelt HJ, and Villems R.2002. The emerging limbs and twigs of the East Asian mtDNA tree. Mol Biol Evol 19: 1737-1751.
25.Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M,Easley K, Chen E, Brown MD et al.2003. Natural selection shaped regional mtDNA variation in humans. Proc Natl Acad Sci U S A 100:171-176.
26.Achilli A, Rengo C, Magri C, Battaglia V, Olivieri A, Scozzari R, Cruciani F, ZevianiM, Briem E, Carelli V et al.2004. The molecular dissection of mtDNA haplogroup H confirms that the Franco-Cantabrian glacial refuge was a major source for the European gene pool. Am J Hum Genet 75:910-918.
27.Macaulay V, Hill C, Achilli A, Rengo C, Clarke D, Meehan W, Blackburn J, SeminoO, Scozzari R, Cruciani F et al.2005. Single, rapid coastal settlement of Asia revealed by analysis of complete mitochondrial genomes. Science 308:1034-1036.
28.Yao YG, Kong QP, and Zhang YP.2002b. Mitochondrial DNA 5178A polymorphismand longevity. Hum Genet 111:462-463.
29.Kong QP, Bandelt HJ, Sun C, Yao YG, Salas A, Achilli A, Wang CY, Zhong L, ZhuCL, Wu SF et al.2006. Updating the East Asian mtDNA phylogeny:a prerequisite for the identification of pathogenic mutations. Hum Mol Genet 15:2076-2086.
30. Yao YG, Salas A, Bravi CM, and Bandelt HJ.2006. A reappraisal of complete mtDNA variation in East Asian families with hearing impairment. Hum Genet 119:505-515.
31.Andrews RM, Kubacka I, Chinnery PF, et al. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet,1999, 23(2):147.
32.Maximo V. J. Lima, P. Soares, et al. Mitochondria and cancer. Virchows Arch,2009, 454(5):481-95.
33.Kong QP, Bandelt HJ, Sun C, et al., Updating the East Asian mtDNA phylogeny:a prerequisite for the identification of pathogenic mutations. Human Molecular Genetics, 2006,15(13):2076-2086.
34.Sun C, Kong QP, Palanichamy MG, Agrawal S, Bandelt HJ, Yao YG, Khan F, Zhu CL,Chaudhuri TK, and Zhang YP.2006. The dazzling array of basal branches inthe mtDNA macrohaplogroup M from India as inferred from completegenomes. Mol Biol Evol 23:683-690.
35.Yao YG, Kong QP, Bandelt HJ, et al. Phylogeographic differentiation of mitochondrial DNA in Han Chinese. Am J Hum Genet,2002,70:635-651.
36.吴祥德,董守义.乳腺疾病诊治[M].北京：人民卫生出版社,2000：216-221.
37.Connolly JL,Schnitt SJ,London S,et al.Both arypical lobular hyperplasia(ALH)and atypical ductal hyperplasia(ADH)predict for bilateral breast cancer risk.Lab Invest,1992,66:13A(abst)
38.Marshall LM,Hunter DJ,ConnollyJL,et al.Risk of breast cancer associated with atypical hyperplasia of lobular and ductaltypes.Cancer Epidemiol Biomarkers Prev,1997,6:297-301
39.Guinebretiere JM,Le Monique G.,Gavoille A,et al.Angiogenesis and risk of breast cancer in women with fibrocystic disease.Nat Cancer Inst,1994,86:635-636
40.McDivitt RW,Stevens JA,Lee NC,et al.Histologic types of benign breast disease and the risk for breast cancer.The cancer and steroid Hormone Study Group.Cancer,2006,69:1408-1414
41.Tseng LM, Yin PH, Chi CW, Hsu CY, Wu CW, Lee LM, Wei YH, and Lee HC. Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer. Genes Chromosomes Cancer,2006,45:629-638.
42.Abu-Amero KK, Alzahrani AS, Zou M, Shi Y. High frequency of somatic mitochondrial DNA mutations in human thyroid carcinomas and complex I respiratory defect in thyroid cancer cell lines. Oncogene,2005,24:1455-1460.
43.Gallardo M.E., R. Moreno-Loshuertos, C. Lopez, et al. m.6267G>A:a recurrent mutation in the human mitochondrial DNA that reduces cytochrome c oxidase activity and is associated with tumors. Hum Mutat,2006,27(6):575-82.
44. Palanichamy MG, Sun C, Agrawal S, Bandelt HJ, Kong QP, Khan F, Wang CY, Chaudhuri TK, Palla V, and Zhang YP. Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing:implications for the peopling of South Asia. Am J Hum Genet,2004,75:966-978.
45.Salas A, Yao YG, Macaulay V, Vega A, Carracedo A, and Bandelt HJ. A critical reassessment of the role of mitochondria in tumorigenesis. PLoS Med,2005,2:e296.
46.Carew JS, Huang P. Mitochondrial defects in cancer. Mol Cancer,2002,1:9.
47.Hibi K, Nakayama H, Yamazaki T, et al. Detection of mitochondrial DNA alterations in primary tumors and corresponding serum of colorectal cancer patients. Int J Cancer, 2001,94(3):429-431.
48. Wang Y,Liu V,W.Tsang P.C.et al.Microsatellite instability in mitochondrial genomeof common femalers.hat J Gynecol Cancer 2006.16 Suppl:259-66.
49. Hacia J.Q,Brody L.C,Chee M.S,et al.Detection of heterozygous mutations in BRCA1 using higll density oligonucleotide arrays and two-colour fluorescence analysis.Nat Genet 1996.14(4):441.7.
50. Shi M.M.Enabling.large·scale pharmacogenetic studies by high-throughput mutation detection and genotypmg technologies.Clin Chem 2001.47(2):164-72.
51.Sharma H,Smgh A,Sharma C,et al.Mutations in the mitochondrial DNA D-loop region are frequent in cervical CanCel.Cancer Cell Int 2005,5:34.
52. Khan SA,Rogers MA,Khurana KK,et al.Estrogen receptor expression in benign breast epithelium and breast cancer risk[see comments].H Natl Cancer Inst,1998,9037-42
53.Gobbi H,Dupont WD,Parl FF,et al.Estrogen receptor expression in epithelial hyperplasia without atypia and breast cancer risk:a nested case control-study.Mod Patblo,2003.16:29A
54. Guinebretiere JM,Le Monique G.,Gavoille A,et al.Angiogenesis and risk of breast cancer in women with fibrocystic disease.I Natl Cancer Inst,1994,86:635-636
55.Heffeli.finger SC,Yassin R,Miller MA,et al.Vascularity of proliferativge breast disease and carcimoma in situ correlates with distological features.Clin Cancer Res, 1996,2:1873-1878.
1.Tanaka M, Ino H, Ohno K, Hattori K, Sato W, Ozawa T, Tanaka T, and Itoyama S.1990. Mitochondrial mutation in fatal infantile cardiomyopathy. Lancet 336:1452.
2.Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, Arnos KS,Cortopassi GA, Jaber L, Rotter JI et al.1993. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness.Nat Genet 4:289-294.
3.Poulton J, Luan J, Macaulay V, Hennings S, Mitchell J, and Wareham NJ.2002. Type2 diabetes is associated with a common mitochondrial variant:evidence from a population-based case-control study. Hum Mol Genet 11:1581-1583.
4. Petros JA, Baumann AK, Ruiz-Pesini E, Amin MB, Sun CQ, Hall J, Lim S, Issa MM,Flanders WD, Hosseini SH et al.2005. mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci U S A 102:719-724.
5. Holt IJ, Harding AE, and Morgan-Hughes JA.1988. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331:717-719.
6. Warburg O.1956. On the origin of cancer cells. Science 123:309-314.
7. Green DR, and Reed JC.1998. Mitochondria and apoptosis. Science 281:1309-1312.
8. Eng C, Kiuru M, Fernandez MJ, and Aaltonen LA.2003. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer 3:193-202.
9. Penta JS, Johnson FM, Wachsman JT, and Copeland WC.2001. Mitochondrial DNA in human malignancy. Mutat Res 488:119-133.
10. Polyak K, Li Y, Zhu H, Lengauer C, Willson JK, Markowitz SD, Trush MA,Kinzler KW, and Vogelstein B.1998. Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet 20:291-293.
11. Habano W, Sugai T, Yoshida T, and Nakamura S.1999. Mitochondrial gene mutation, but not large-scale deletion, is a feature of colorectal carcinomas with mitochondrial microsatellite instability. Int J Cancer 83:625-629.
12. Fliss MS, Usadel H, Caballero OL, Wu L, Buta MR, Eleff SM, Jen J, and Sidransky D.2000. Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science 287:2017-2019.
13. Hibi K, Nakayama H, Yamazaki T, Takase T, Taguchi M, Kasai Y, Ito K, Akiyama S,and Nakao A.2001. Detection of mitochondrial DNA alterations in primary tumors and corresponding serum of colorectal cancer patients. Int J Cancer94:429-431.
14. Abnet CC, Huppi K, Carrera A, Armistead D, McKenney K, Hu N, Tang ZZ, Taylor PR, and Dawsey SM.2004. Control region mutations and the 'common deletion' are frequent in the mitochondrial DNA of patients with esophageal squamous cell carcinoma. BMC Cancer 4:30.
15. Aikhionbare FO, Khan M, Carey D, Okoli J, and Go R.2004. Is cumulative frequency of mitochondrial DNA variants a biomarker for colorectal tumor progression? Mol Cancer 3:30.
16. Kumimoto H, Yamane Y, Nishimoto Y, Fukami H, Shinoda M, Hatooka S, and Ishizaki K.2004. Frequent somatic mutations of mitochondrial DNA in esophageal squamous cell carcinoma. Int J Cancer 108:228-231.
17. Linnartz B, Anglmayer R, and Zanssen S.2004. Comprehensive scanning of somatic mitochondrial DNA alterations in acute leukemia developing from myelodysplastic syndromes. Cancer Res 64:1966-1971.
18. Kong QP.2005. Phylogenomics research in mitochondrial DNA in East Asiapopulation. Graduate School of the Chinese Academy of Sciences DoctoralDissertation.
19. Wallace DC.1994. Mitochondrial DNA sequence variation in human evolution and disease. Proc Natl Acad Sci U S A 91:8739-8746.
20. Wallace DC, Brown MD, and Lott MT.1999. Mitochondrial DNA variation in human evolution and disease. Gene 238:211-230.
21. Torroni A, Campos Y,Rengo C,Sellitto D, Achilli A, Magri C, Semino O, Garcia A Jara P, Arenas J et al.2003. Mitochondrial DNA haplogroups do not play a role in the variable phenotypic presentation of the A3243G mutation. Am J Hum Genet 72: 1005-1012.
22.Wunderlich V.Schutt M,Bottger M.et al.Preferential alkylation of mitochondrial deoxyribonucleic acid by N.methyl.N.nitroeourea[J].Biochem,1970,118(1):9-109.
23.Backer J M.Weinstein B.Mitechondrial DNA is a major cellular target for adihydrodiol-epoxlde derivative of benzopyrene[J].Science,1980,209(4 453):297-299.
24.Howad T.Jacobs Disorders of mitechondrial protein synthesis [J].Human Molecular Genetics.2003,12(2):293-301.
25.Parrcfla P,Xiao Y,Fliss M,et al.Detection of mitechoodrial DNA mutations in primary breast cancer and fine needle&spimtes[J],caner Res,2001,61(20):7623-7626.
26.Zhu W,Qin W,Sauter E R,Largescale mitochondrial DNA detetion mutations and nuclear genome instability in human breast cancer [J]. Cancer Detect Prey,2004,28(2): 119-126.
27.周云丽,牛瑞芳,史玉荣.乳腺癌线粒体基因组控制区突变的研究[J],中华肿瘤防治杂志,2006,13(14)：1082-1084.
28.谭端军,刘玲玲,白仁奎,等.中国人乳腺癌患者线粒体基因体细胞性突变[J].肿瘤防治研究,2003,30(5)：341-345.
29. Wang Y,Hu Vw,Ngan HY,et al.Frequent occurrence of mitochon drial micmsatellite instability in the d-loop re#on of human cancers [J].Ann N Y Acad Sci,2005,1 042:123-129.
30.Tan DJ.nfluence of instability of mitochondrial genme length on tumorigcnesis in humen tumors [J]中国临床康复,2004,17(8)：3410-3413.
31.Zhu W,Qin W,Bradley P,et al.Mitechondrial DNA mutations in breast cancer tissue and in matched nipple aspirate fluid[J].Careinogenesis,2005,26(1):145-152.
32.靳斌,任军,张亮,等.变性高效液相色谱检测乳腺癌患者血浆线粒体D环HVR2突变[J].第四军医大学学报,2003,24(10)：911-913.
33.周云丽,牛瑞芳,史玉荣,等.乳腺癌线粒体DNA拷贝数改变的研究及意义[J].天滓医科大学学报,2005,11(4)：525-527.
2. Andrews, R.M., I. Kubacka, P.F. Chinnery, R.N. Lightowlers, D.M. Turnbull, and N. Howell. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet,1999,23(2):147.
3. Anderson, S., A.T. Bankier, B.G. Barrell, M.H. de Bruijn, A.R. Coulson, J. Drouin, I.C. Eperon, D.P. Nierlich, B.A. Roe, F. Sanger, P.H. Schreier, A.J. Smith, R. Staden, and I.G. Young. Sequence and organization of the human mitochondrial genome. Nature, 1981,290(5806):457-65.
4. Fliss MS, Usadel H, Caballero OL, et al. Facile Detection of Mitochondrial DNA Mutations in Tumors and Bodily Fluids. Science,2000,287(5460):2017-2019.
5.Chen J Z, Gokdem N, Green G F, et al. SilIlultaneondrial generation of multiple mitochondrial DNA mutations in humam prostate tumors suggests mitochondrial hyper-mutagenesis. Caminogenesis,2003,24(9):1481-1487.
6.Kiches E, Mawrin C, Schneider Stock R et al. Mitochondrial DNA as a clonal tumor marker:glimatosis cerebri. J Neurooncol,2003,61(1):1-5.
7. Bianchi NO, Bianchi MS, Richard SM. Mitochondrial genome instability in human cancers. Mutat Res,2001,488:9-23.
8.Richard SM, Bailliet G, Paez GL, et al. Nuclear and mitochondrial genome instability in human breast cancer. Cancer Res,2000,60:4231-4237.
9.Suzuki M, Toyooka S, Miyajima K, et al. Alterations in the mitochondrial displacement loop in lung cancers. Clin Cancer Res,2003,9:5636-5641.
10. Warburg O. On the Origin of Cancer Cells. Science,1956,123(3191):309-314
11. Lievre A, Chapusot C, Bouvier AM, et al. Clinical value of mitochondrial mutations in colorectal cancer. J Clin Oncol,2005,23:3517-3525.
12. Tan DJ, Bai RK, Wong LJ. Comprehensive scanning of somatic mitochondrial DNA mutations in breast cancer. Cancer Res 2002,62:972-976.
13. Polyak K, Li Y, Zhu H, et al. Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet,1998,20(3):291-293.
14. Liu VW, Shi HH, Cheung AN, Chiu PM, Leung TW, Nagley P, Wong LC, Ngan HY. High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas. Cancer Res 2001,61:5998-6001.
15. liss MS, Usadel H, Caballero OL, et al. Facile Detection of Mitochondrial DNA Mutations in Tumors and Bodily Fluids. Science,2000,287(5460):2017-2019.
16. Wu CW, Yin PH, Hung WY, Li AF, Li SH, Chi CW, Wei YH, Lee HC. Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosomes Cancer 2005,44:19-28.
17. Nishikawa M, Nishiguchi S, Shiomi S, Tamori A, Koh N, Takeda T, Kubo S, Hirohashi K, Kinoshita H, Sato E, Inoue M. Somatic mutation of mitochondrial DNA in cancerous and noncancerous liver tissue in individuals with hepatocellular carcinoma. Cancer Res 2001,61:1843-1845.
18. Jeronimo C, Nomoto S, Caballero OL, Usadel H, Henrique R, Varzim G, Oliveira J, Lopes C, Fliss MS, Sidransky D. Mitochondrial mutations in early stage prostate cancer and bodily fluids. Oncogene 2001,20:5195-5198.
19. Petros JA, Baumann AK, Ruiz-Pesini E, et al. mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci USA,2005,102(3):719-724.
20. Abu-Amero KK, Alzahrani AS, Zou M, Shi Y. High frequency of somatic mitochondrial DNA mutations in human thyroid carcinomas and complex I respiratory defect in thyroid cancer cell lines. Oncogene 2005,24:1455-1460.
21. Hibi K, Nakayama H, Yamazaki T, et al. Detection of mitochondrial DNA alterations in primary tumors and corresponding serum of colorectal cancer patients. Int J Cancer, 2001,94(3):429-431.
22. Sanchez-Cespedes M, Parrella P, Nomoto S, Cohen D, Xiao Y, Esteller M, Jeronimo C, Jordan RC, Nicol T, Koch WM, Schoenberg M, Mazzarelli P, et al. Identification of a mononucleotide repeat as a major target for mitochondrial DNA alterations in human tumors. Cancer Res 2001,61:7015-7019.
23. Carew JS, Huang P. Mitochondrial defects in cancer. Mol Cancer 2002,1:9.
24. Chatterjee A, Mambo E, Sidransky D. Mitochondrial DNA mutations in human cancer. Oncogene 2006,25:4663-4674.
25. Brandon M, Baldi P, Wallace DC. Mitochondrial mutations in cancer. Oncogene 2006, 25:4647-4662.
26. Canter JA, Kallianpur AR, Parl FF, Millikan RC. Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res 2005,65:8028-8033.
27. Liu VW, Wang Y, Yang HJ, Tsang PC, Ng TY, Wong LC, Nagley P, Ngan HY. Mitochondrial DNA variant 16189T>C is associated with susceptibility to endometrial cancer. Hum Mutat 2003,22:173-174.
28. Jakupciak JP, Dakubo GD, Maragh S, Parr RL. Analysis of potential cancer biomarkers in mitochondrial DNA. Curr Opin Mol Ther 2006,8:500-506.
29. Nomoto S, Yamashita K, Koshikawa K, Nakao A, Sidransky D. Mitochondrial D-loop mutations as clonal markers in multicentric hepatocellular carcinoma and plasma. Clin Cancer Res 2002,8:481-487.
30. Beckman KB, and Ames BN. Oxidative decay of DNA. J Biol Chem,1997, 272:19633-19636.
31. Stoneking M. Hypervariable sites in the mtDNA control region are mutational hotspots. Am J Hum Genet,2000,67:1029-1032.
32. Vanecek T, Vorel F, and Sip M. Mitochondrial DNA D-loop hypervariable regions: Czech population data. Int J Legal Med,2004,118:14-18.
33.Zhu w, Qin w, Bradley P'Wessel A, Puckett CL, Sauter ER. M itochondrial DNA mutations in breast cancer tissue and in matched nipple aspirate fluid. Carcinogenesis, 2005,26(1):145-152.
34. Holt IJ, Harding AE, and Morgan-Hughes JA.1988. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331:717-719.
35. Nomoto S,et al. Mitochondrial D-Loop Mutation As Clonal Markers in Multicentric hepatocellular Carcinoma and Plasma J. Clin Cancer Res,2002.8(2):481-487.
36. Wang CY, Wang HW, Yao YG, et al. Somatic mutations of mitochondrial genome in early stage breast cancer. Int J Cancer,2007,121:1253-1256.
37. Yao YG, Kong QP, Bandelt HJ, et al. Phylogeographic differentiation of mitochondrial DNA in Han Chinese. Am J Hum Genet,2002,70:635-651.
38.蒋学祥,王霄英.正确发挥影像学在乳腺癌诊治中的作用.中华放射学杂志,2010,44(5).453.
39.中华人民共和国卫生部.第三次全国死因调查主要情况.中国肿瘤,2008,17(5)：344-345.
40.沈镇宇,邵志敏.现代乳腺肿瘤学进展.上海,上海科学技术文献出版社.2002.3-5.
41.Jeong H C, Kim J A, ImHH, et al. Mitochondrial DNA sequence variation of the swallow tail, butterfly, papilio xuthus。and the cabbage butterfly, pieris rapae J. Biochem Genet,2009,29. [E pub ahead of print].
42.Rojas M,Gonzalez I.Fajardo C,et al. Polymerase chain reaction- restriction fragment length polymorp hismau thentication of raw meats from game birds[J].J AoAC Int,2008,91:1416-1422.
43. Sehinogl P,Muller M,Steinborn R.Quantification of the 4977-bp deletion in human mitochondrial DNA usingreal-time PCR[J]. Forensic Sci Int,2001,122:197-199.
44. Paez G,Richard S, Bianchi MS, et al. Loss of heterozygosity (LOH) in 15q26.2 in breast cancer. Mutat Res,2001,484:103-106.
45.谭端军,刘玲玲,徐斌等.中国汉族人与美国高加索人乳腺癌患者线粒体基因组突变的比较.中国临床康复,2005,9：114-116.
46.Wang Y, Liu VW, Tsang PC, et al. Microsatellite instability in mitochondrial genome of common female cancers. Int J Gynecol Cancer,2006,16(Suppl 1):259-266.
47.Cavelier L, Jazin E, Jalonen P, and Gyllensten U.2000. MtDNA substitution rate andsegregation of heteroplasmy in coding and noncoding regions. Hum Genet107:45-50.
48. Wallace DC.1994. Mitochondrial DNA sequence variation in human evolution anddisease. Proc Natl Acad Sci U S A 91:8739-8746.
49.Croteau DL, and Bohr VA.1997. Repair of oxidative damage to nuclear andmitochondrial DNA in mammalian cells. J Biol Chem 272:25409-25412.
50.Yao YG, Kong QP, Wang CY, et al. Different matrilineal contributions to genetic structure of ethnic groups in the silk road region in China. Mol Biol Evol,2004, 21:2265-2280.
51.Kong QP, Yao Y, Sun C, et al. Phylogeny of east Asian mitochondrial DNA lineages inferred from complete sequences. Am J Hum Genet,2003,73:671-676.
52.Sun C, Kong QP, Palanichamy MG, et al. The dazzling array of basal branches in the mtDNA macrohaplogroup M from India as inferred from complete genomes. Mol Biol Evol,2006,23:683-690.
53. Penta JS,Johnson FM.Wachsman JT.et al.Mitochondfial DNA in human malignancy.Murat Res,2001,488:119-133.
54.DiMauto S.Schon EA.Mitochondfial DNA mutations in human disease.Am J Med Genet.2001.106:18-26.
55. Poetsch M,Petersmann A,Lignitz E,et al.Relationship between mitochondfial DNA instability,mitochondrial DNA large deletions,and nuclear microsatellite instability in head and neck sqnamous cell carcinomas. Diagn Mel Patllel,2004,13:26-32.
56. Hiyama T,Tanaka S.Shima H.et al.Somatic mutation in mitochondrial DNA and nuclear mien satellite instability in gastric cancer.Oncol Rep.2003.10:1837-1841.
57. Lutz S, Weisser HJ, Heizmann J, and Pollak S.1998. Location and frequency ofpolymorphic positions in the mtDNA control region of individuals fromGermany. Int J Legal Med 111:67-77.
58Jones JB, Song JJ, Hempen PM, Parmigiani G, Hruban RH, and Kern SE. 2001.Detection of mitochondrial DNA mutations in pancreatic cancer offers a"mass"-ive advantage over detection of nuclear DNA mutations. Cancer Res61:1299-1304.
59.Chinnery PF,Samuels DC,Elson J, and Turnbull DM.2002. Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease:is there a common mechanism? Lancet 360:1323-1325.
60.Zhu W,Qin w,Sauter ER.Large-scale mitochondrial DNA deletion mu tations and nuclear genome instability in human breast cancer. Cancer Detect Prev, 2004.28:119.126.
61.Lee HC,Yin PH, Lin JC,et al. Mitochondrial genome instability and mtDNA depletion in human cancers. Ann N Y Acad Sci,2005,1042:109-122.
62.Zhao YB,Yang HY,Zhang XW,et al. Mutation in D-loop region of mitochondrial DNA in gastric cancer and its significance. Work J Castroenterol,2005,11:3304-3306.
63.Rosson D, Keshgegian AA. Frequent mutations in the mitochondrial control region DNA in breast tissue. Cancer Lett,2004,215:89-94.
64.Liane Fendt, Bettina Zimmermann, Martin Daniaux, et al. Sequencing strategy for the whole mitochondrial genome resulting in high quality sequences. BMC Genomics, 2009,10:139.
65.Coller,H.A,K. Khrapko,N.D. Bodyak, E. Nekhaeva, P. Herrero-Jimenez, and W.G. Thilly. High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection. Nat Genet,2001,28(2):147-50.
66.Poetsch M,Petersmann A, Lignitz E,et al.Relationship between mitochondfial DNA instability,mitochondrial DNA large deletions, and nuclear microsatellite instability in head and neck sqnamous cell carcinomas. Diagn Mel Patllel,2004,13:26-32.
67. Hiyama T,Tanaka S.Shima H.et al.Somatic mutation in mitochondrial DNA and nuclear mien)satellite instability in gastric cancer.Oncol Rep2003.10:1837-1841.
68. Perou CM, Sodie T, Eisin MB, et a. Mdecular portraits of human breast tumours[J]. Nature,2000,406(6797):747-752.
69. Nielsen TO,-lsu FD,ensen K,et and clinical characterization of the basal-like subtype Of invasive breast carcinoma[J.]Clin Cancer Res,2004,10(6):5367-5374.
1.陈丽芹,王徐东,张子和等.乳腺疾病的相关因素及防治措施.中国综合临床,(6)2007,23：563.
2.Kronowitz SJ.Robb CL.Breaat reconstruction with p06tmaatectomy radiation therapy: onuuent issues[J]. Plast Reconstr Surg,2004,114(4):950-960.
3.AJchazalak SK, Suuy L, Fallowfield L,et al.The Psychological im. pact Of immediate rather than delayed breconstmction[J].Eur J Surg Oncol,2000,26(1):17-19.
4.李云英.乳腺纤维腺瘤癌变.中国肿瘤临床,1994,21：760.
5.吴祥德,董守义.乳腺疾病诊治.人民卫生出版社,2009：166-168.
6.龚畅,苏逢锡.良性乳腺病的概念转变[J].国外医学外科分册,2004,31：145-148.
7.Bodian CA,Perzin KH,Lattes R,et al.Prognostic significance of benign proliferative breast disease,Cancer,2005,71:3896-3907.
8.Marshall LM,Hunter DJ,ConnollyJL,et al.Risk of breast cancer associated with atypical hyperplasia of lobular and ductaltypes.Cancer Epidemiol Biomarkers Prev, 1997,6:297-301.
9.Dupont WD,Page DL.Risk factors for breast cancer in women with proliferative breast disease.N Engl J Med,2007,312:146-151.
10.Page KL,Dupont WD,Rogers LW,et al,Atypical thperplastic lesions of the female breast:a long-term follow-uo study.Cancer,2006,55:2698-2708.
11.Kodlin D,Winger EE,Morgenstem NL,et al.Chronic mastopathy and breast cancer:a follow-up study.Cancer,1997,39:2603-2607.
12.Carter CL,Corle DK,Micozzi MS,et al.A prospective study of the development of breast cancer in 16692 women with benign breast disease.Am I Epidemiol,1988, 128:467-477.
13.Tacassoli FA,Norris HJ.A comparison of the results of longterm follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast.Cancer,1990, 65:518-529.
14.Palli D,Rosselli del Turco M,simoncini R,et al.Benign breast disease and breast cancer:a case-control study in a cohort in Italy.Int J Cancer,1991,47:703-706.
15.Lindon SJ,Connolly JL,Schnitt SJ,et al.A prospective study of benign breast disease and the risk of breast cancer.JAMA,2006,267:941-944.
16.Krieger N,.Hiatt RA.Risk of breast cancer after benign bresat diseases:variation by histologic type,degree of atypia,age at biopsy,and length of follow-up. Am J Epidemiol, 2007,135:619-631.
17.Parrella P,Liao Y,Hiss M,et al.Detection of mitochondrial DNA mutations in primary breast CanCer and fine-needle aspirates.Cancer Res 2001,61(20):7623-6.
18.周云丽,牛瑞芳,史玉荣等.乳腺癌线粒体DNA拷贝数改变的研究及意义.中华肿瘤防治杂志2006.13(14)：1082-84.
19.Bandelt HJ,Lahermo P,Richards M,and Macaulay V.2001.Detecting errors in mtDNA data by phylogenetic analysis. Int J Legal Med 115:64-69.
20.Bandelt HJ, Achilli A, Kong QP, Salas A, Lutz-Bonengel S, Sun C, Zhang YP, TorroniA, and Yao YG.2005a. Low "penetrance" of phylogenetic knowledge in mitochondrial disease studies. Biochem Biophys Res Commun 333:122-130.
21.Bandelt HJ, Kong QP, Parson W, and Salas A.2005b. More evidence for non-maternalinheritance of mitochondrial DNA J Med Genet 42:957-960.
22.Ingman M, Kaessmann H, Paabo S, and Gyllensten U.2000. Mitochondrial genomevariation and the origin of modern humans. Nature 408:708-713.
23.Maca-Meyer N,Gonzalez AM,Larruga JM,Flores C,and Cabrera VM.2001. Major genomic mitochondrial lineages delineate early human expansions. BMC Genet 2:13.
24.Kivisild T, Tolk HV, Parik J, Wang Y, Papiha SS, Bandelt HJ, and Villems R.2002. The emerging limbs and twigs of the East Asian mtDNA tree. Mol Biol Evol 19: 1737-1751.
25.Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M,Easley K, Chen E, Brown MD et al.2003. Natural selection shaped regional mtDNA variation in humans. Proc Natl Acad Sci U S A 100:171-176.
26.Achilli A, Rengo C, Magri C, Battaglia V, Olivieri A, Scozzari R, Cruciani F, ZevianiM, Briem E, Carelli V et al.2004. The molecular dissection of mtDNA haplogroup H confirms that the Franco-Cantabrian glacial refuge was a major source for the European gene pool. Am J Hum Genet 75:910-918.
27.Macaulay V, Hill C, Achilli A, Rengo C, Clarke D, Meehan W, Blackburn J, SeminoO, Scozzari R, Cruciani F et al.2005. Single, rapid coastal settlement of Asia revealed by analysis of complete mitochondrial genomes. Science 308:1034-1036.
28.Yao YG, Kong QP, and Zhang YP.2002b. Mitochondrial DNA 5178A polymorphismand longevity. Hum Genet 111:462-463.
29.Kong QP, Bandelt HJ, Sun C, Yao YG, Salas A, Achilli A, Wang CY, Zhong L, ZhuCL, Wu SF et al.2006. Updating the East Asian mtDNA phylogeny:a prerequisite for the identification of pathogenic mutations. Hum Mol Genet 15:2076-2086.
30. Yao YG, Salas A, Bravi CM, and Bandelt HJ.2006. A reappraisal of complete mtDNA variation in East Asian families with hearing impairment. Hum Genet 119:505-515.
31.Andrews RM, Kubacka I, Chinnery PF, et al. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet,1999, 23(2):147.
32.Maximo V. J. Lima, P. Soares, et al. Mitochondria and cancer. Virchows Arch,2009, 454(5):481-95.
33.Kong QP, Bandelt HJ, Sun C, et al., Updating the East Asian mtDNA phylogeny:a prerequisite for the identification of pathogenic mutations. Human Molecular Genetics, 2006,15(13):2076-2086.
34.Sun C, Kong QP, Palanichamy MG, Agrawal S, Bandelt HJ, Yao YG, Khan F, Zhu CL,Chaudhuri TK, and Zhang YP.2006. The dazzling array of basal branches inthe mtDNA macrohaplogroup M from India as inferred from completegenomes. Mol Biol Evol 23:683-690.
35.Yao YG, Kong QP, Bandelt HJ, et al. Phylogeographic differentiation of mitochondrial DNA in Han Chinese. Am J Hum Genet,2002,70:635-651.
36.吴祥德,董守义.乳腺疾病诊治[M].北京：人民卫生出版社,2000：216-221.
37.Connolly JL,Schnitt SJ,London S,et al.Both arypical lobular hyperplasia(ALH)and atypical ductal hyperplasia(ADH)predict for bilateral breast cancer risk.Lab Invest,1992,66:13A(abst)
38.Marshall LM,Hunter DJ,ConnollyJL,et al.Risk of breast cancer associated with atypical hyperplasia of lobular and ductaltypes.Cancer Epidemiol Biomarkers Prev,1997,6:297-301
39.Guinebretiere JM,Le Monique G.,Gavoille A,et al.Angiogenesis and risk of breast cancer in women with fibrocystic disease.Nat Cancer Inst,1994,86:635-636
40.McDivitt RW,Stevens JA,Lee NC,et al.Histologic types of benign breast disease and the risk for breast cancer.The cancer and steroid Hormone Study Group.Cancer,2006,69:1408-1414
41.Tseng LM, Yin PH, Chi CW, Hsu CY, Wu CW, Lee LM, Wei YH, and Lee HC. Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer. Genes Chromosomes Cancer,2006,45:629-638.
42.Abu-Amero KK, Alzahrani AS, Zou M, Shi Y. High frequency of somatic mitochondrial DNA mutations in human thyroid carcinomas and complex I respiratory defect in thyroid cancer cell lines. Oncogene,2005,24:1455-1460.
43.Gallardo M.E., R. Moreno-Loshuertos, C. Lopez, et al. m.6267G>A:a recurrent mutation in the human mitochondrial DNA that reduces cytochrome c oxidase activity and is associated with tumors. Hum Mutat,2006,27(6):575-82.
44. Palanichamy MG, Sun C, Agrawal S, Bandelt HJ, Kong QP, Khan F, Wang CY, Chaudhuri TK, Palla V, and Zhang YP. Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing:implications for the peopling of South Asia. Am J Hum Genet,2004,75:966-978.
45.Salas A, Yao YG, Macaulay V, Vega A, Carracedo A, and Bandelt HJ. A critical reassessment of the role of mitochondria in tumorigenesis. PLoS Med,2005,2:e296.
46.Carew JS, Huang P. Mitochondrial defects in cancer. Mol Cancer,2002,1:9.
47.Hibi K, Nakayama H, Yamazaki T, et al. Detection of mitochondrial DNA alterations in primary tumors and corresponding serum of colorectal cancer patients. Int J Cancer, 2001,94(3):429-431.
48. Wang Y,Liu V,W.Tsang P.C.et al.Microsatellite instability in mitochondrial genomeof common femalers.hat J Gynecol Cancer 2006.16 Suppl:259-66.
49. Hacia J.Q,Brody L.C,Chee M.S,et al.Detection of heterozygous mutations in BRCA1 using higll density oligonucleotide arrays and two-colour fluorescence analysis.Nat Genet 1996.14(4):441.7.
50. Shi M.M.Enabling.large·scale pharmacogenetic studies by high-throughput mutation detection and genotypmg technologies.Clin Chem 2001.47(2):164-72.
51.Sharma H,Smgh A,Sharma C,et al.Mutations in the mitochondrial DNA D-loop region are frequent in cervical CanCel.Cancer Cell Int 2005,5:34.
52. Khan SA,Rogers MA,Khurana KK,et al.Estrogen receptor expression in benign breast epithelium and breast cancer risk[see comments].H Natl Cancer Inst,1998,9037-42
53.Gobbi H,Dupont WD,Parl FF,et al.Estrogen receptor expression in epithelial hyperplasia without atypia and breast cancer risk:a nested case control-study.Mod Patblo,2003.16:29A
54. Guinebretiere JM,Le Monique G.,Gavoille A,et al.Angiogenesis and risk of breast cancer in women with fibrocystic disease.I Natl Cancer Inst,1994,86:635-636
55.Heffeli.finger SC,Yassin R,Miller MA,et al.Vascularity of proliferativge breast disease and carcimoma in situ correlates with distological features.Clin Cancer Res, 1996,2:1873-1878.
1.Tanaka M, Ino H, Ohno K, Hattori K, Sato W, Ozawa T, Tanaka T, and Itoyama S.1990. Mitochondrial mutation in fatal infantile cardiomyopathy. Lancet 336:1452.
2.Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, Arnos KS,Cortopassi GA, Jaber L, Rotter JI et al.1993. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness.Nat Genet 4:289-294.
3.Poulton J, Luan J, Macaulay V, Hennings S, Mitchell J, and Wareham NJ.2002. Type2 diabetes is associated with a common mitochondrial variant:evidence from a population-based case-control study. Hum Mol Genet 11:1581-1583.
4. Petros JA, Baumann AK, Ruiz-Pesini E, Amin MB, Sun CQ, Hall J, Lim S, Issa MM,Flanders WD, Hosseini SH et al.2005. mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci U S A 102:719-724.
5. Holt IJ, Harding AE, and Morgan-Hughes JA.1988. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331:717-719.
6. Warburg O.1956. On the origin of cancer cells. Science 123:309-314.
7. Green DR, and Reed JC.1998. Mitochondria and apoptosis. Science 281:1309-1312.
8. Eng C, Kiuru M, Fernandez MJ, and Aaltonen LA.2003. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer 3:193-202.
9. Penta JS, Johnson FM, Wachsman JT, and Copeland WC.2001. Mitochondrial DNA in human malignancy. Mutat Res 488:119-133.
10. Polyak K, Li Y, Zhu H, Lengauer C, Willson JK, Markowitz SD, Trush MA,Kinzler KW, and Vogelstein B.1998. Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet 20:291-293.
11. Habano W, Sugai T, Yoshida T, and Nakamura S.1999. Mitochondrial gene mutation, but not large-scale deletion, is a feature of colorectal carcinomas with mitochondrial microsatellite instability. Int J Cancer 83:625-629.
12. Fliss MS, Usadel H, Caballero OL, Wu L, Buta MR, Eleff SM, Jen J, and Sidransky D.2000. Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science 287:2017-2019.
13. Hibi K, Nakayama H, Yamazaki T, Takase T, Taguchi M, Kasai Y, Ito K, Akiyama S,and Nakao A.2001. Detection of mitochondrial DNA alterations in primary tumors and corresponding serum of colorectal cancer patients. Int J Cancer94:429-431.
14. Abnet CC, Huppi K, Carrera A, Armistead D, McKenney K, Hu N, Tang ZZ, Taylor PR, and Dawsey SM.2004. Control region mutations and the 'common deletion' are frequent in the mitochondrial DNA of patients with esophageal squamous cell carcinoma. BMC Cancer 4:30.
15. Aikhionbare FO, Khan M, Carey D, Okoli J, and Go R.2004. Is cumulative frequency of mitochondrial DNA variants a biomarker for colorectal tumor progression? Mol Cancer 3:30.
16. Kumimoto H, Yamane Y, Nishimoto Y, Fukami H, Shinoda M, Hatooka S, and Ishizaki K.2004. Frequent somatic mutations of mitochondrial DNA in esophageal squamous cell carcinoma. Int J Cancer 108:228-231.
17. Linnartz B, Anglmayer R, and Zanssen S.2004. Comprehensive scanning of somatic mitochondrial DNA alterations in acute leukemia developing from myelodysplastic syndromes. Cancer Res 64:1966-1971.
18. Kong QP.2005. Phylogenomics research in mitochondrial DNA in East Asiapopulation. Graduate School of the Chinese Academy of Sciences DoctoralDissertation.
19. Wallace DC.1994. Mitochondrial DNA sequence variation in human evolution and disease. Proc Natl Acad Sci U S A 91:8739-8746.
20. Wallace DC, Brown MD, and Lott MT.1999. Mitochondrial DNA variation in human evolution and disease. Gene 238:211-230.
21. Torroni A, Campos Y,Rengo C,Sellitto D, Achilli A, Magri C, Semino O, Garcia A Jara P, Arenas J et al.2003. Mitochondrial DNA haplogroups do not play a role in the variable phenotypic presentation of the A3243G mutation. Am J Hum Genet 72: 1005-1012.
22.Wunderlich V.Schutt M,Bottger M.et al.Preferential alkylation of mitochondrial deoxyribonucleic acid by N.methyl.N.nitroeourea[J].Biochem,1970,118(1):9-109.
23.Backer J M.Weinstein B.Mitechondrial DNA is a major cellular target for adihydrodiol-epoxlde derivative of benzopyrene[J].Science,1980,209(4 453):297-299.
24.Howad T.Jacobs Disorders of mitechondrial protein synthesis [J].Human Molecular Genetics.2003,12(2):293-301.
25.Parrcfla P,Xiao Y,Fliss M,et al.Detection of mitechoodrial DNA mutations in primary breast cancer and fine needle&spimtes[J],caner Res,2001,61(20):7623-7626.
26.Zhu W,Qin W,Sauter E R,Largescale mitochondrial DNA detetion mutations and nuclear genome instability in human breast cancer [J]. Cancer Detect Prey,2004,28(2): 119-126.
27.周云丽,牛瑞芳,史玉荣.乳腺癌线粒体基因组控制区突变的研究[J],中华肿瘤防治杂志,2006,13(14)：1082-1084.
28.谭端军,刘玲玲,白仁奎,等.中国人乳腺癌患者线粒体基因体细胞性突变[J].肿瘤防治研究,2003,30(5)：341-345.
29. Wang Y,Hu Vw,Ngan HY,et al.Frequent occurrence of mitochon drial micmsatellite instability in the d-loop re#on of human cancers [J].Ann N Y Acad Sci,2005,1 042:123-129.
30.Tan DJ.nfluence of instability of mitochondrial genme length on tumorigcnesis in humen tumors [J]中国临床康复,2004,17(8)：3410-3413.
31.Zhu W,Qin W,Bradley P,et al.Mitechondrial DNA mutations in breast cancer tissue and in matched nipple aspirate fluid[J].Careinogenesis,2005,26(1):145-152.
32.靳斌,任军,张亮,等.变性高效液相色谱检测乳腺癌患者血浆线粒体D环HVR2突变[J].第四军医大学学报,2003,24(10)：911-913.
33.周云丽,牛瑞芳,史玉荣,等.乳腺癌线粒体DNA拷贝数改变的研究及意义[J].天滓医科大学学报,2005,11(4)：525-527.