宁夏地区回、汉族乳腺癌BRCA1基因突变分析
|
摘要
目的BRCA1是遗传性乳腺癌和卵巢癌易感基因(hereditary breast and ovarian cancer susceptibility gene)之一,本实验研究宁夏地区回、汉族乳腺癌患者BRCA1基因突变情况及突变位置。探讨宁夏地区回、汉族人群乳腺癌与BRCA1基因突变的关系,同时分析回、汉族乳腺癌BRCA1基因突变的特点。
方法(1)样本来源:收集宁夏地区乳腺癌患者全血标本130例(回族40例,汉族90例),对照组80例(汉族50例,回族30例)。回族要求三代保留其民族遗传、地域、风俗、文化和生活背景;(2)实验方法:本课题采用PCR直接测序法(PCR:Polymerase Chain Reaction聚合酶链反应)检测汉族、回族及同一地区无肿瘤病史的正常对照者的BRCA1基因突变情况;(3)实验数据统计处理运用SPSS13.0统计软件包,其中率的检验采用卡方检验。免疫组化结果分析采用Mann-Whitney检验,各因素与BRCA1基因突变相关性乳腺癌统计采用非条件Logistic回归。以α=0.05为检验水准。
结果(1) 130例乳腺癌中共发现15例BRCA1基因突变,4例突变在乳腺癌信息中心网站BIC(Breast Cancer Information Core)有报道,2例11号外显子2201C> T突变,1例11号外显子2548del A,1例11号外显子2754 G>A ,11例BRCA1基因碱基突变国内外未见报道,分别为2号外显子的错义突变1例(139G>T),20号外显子的错义突变1例(5317A> T),11号外显子错义突变5例(分别为2403 A> G,2405A>T,943 G>A,981A>G,984 A>T),11号外显子移码突变4例(分别为2722delC,3126insT,944delC,944delC);(2) 130例乳腺癌BRCA1外显子总的突变率为11.54% (15/130),其中90例汉族乳腺癌中有12例发生突变,基因突变率13.33%(12/90),40例回族乳腺癌中有3例发生突变,基因突变率为7.5%(3/40),汉族乳腺癌基因突变率为13.33%(12/90)高于回族乳腺癌基因突变率7.5%(3/40),两者相比经统计学分析无显著性差异(χ2=0.923,P>0.05);(3)130例回、汉族乳腺癌患者中,49例早发性乳腺癌(≤35岁) BRCA1基因突变率为20.4%(10/49)。早发性乳腺癌BRCA1基因突变率(10/ 49)高于晚发性乳腺癌BRCA1基因突变率6.2%(5/81) ,差异有统计学意义(χ2 =6.061 , P < 0. 05) ;(4)15例BRCA1基因突变的乳腺癌中有10例为ER(雌激素受体)阴性、PR(孕激素受体)阴性、人表皮生长因子受体2(HER-2)阴性,即三阴乳腺癌,其比例为66.7%(10/15),而非BRCA1基因突变的乳腺癌中三阴比例为25.2%(29/115),经统计学分析有显著性差异(χ2=10.852 , P < 0.05) ;(5)BRCA1基因突变相关性乳腺癌淋巴结转移率为93.33%(14/15),高于非BRCA1基因突变相关性乳腺癌61.74%(71/115),差异有统计学意义(χ2 =5.852,P<0.05 )。
结论(1)BRCA1基因突变与乳腺癌有密切关系;(2)宁夏地区回、汉族乳腺癌BRCA1基因突变率无明显差异;(3)本研究发现15例突变,其中4例与已有的文献报道一致,11例乳腺癌的10种突变位点均为首次发现,未发现中国人群的“始祖突变”;(4)BRCA1基因突变相关性乳腺癌与非突变对照组相比,具有肿瘤组织学分级III级比例高,ER、PR、CerbB-2阴性率增高的趋势,提示BRCA1基因突变与免疫组化特点存在相关;(5)早发性乳腺癌的发生与BRCA1基因突变有关;(6)BRCA1基因突变相关性乳腺癌更容易发生淋巴结转移,且提示预后较差。
Objective To analyze the mutations of BRCA1 in breast cancer patients in Ningxia. BRCA1 is a hereditary breast and ovarian cancer susceptibility gene (hereditary breast and ovarian cancer susceptibility gene), this experimental study breast cancer patient BRCA1 gene mutation situation and the mutation site of hui and han people in Ningxia.Discuss the relationship between BRCA1 gene mutation and breast cancer, simultaneously analyze the breast cancer BRCA1 gene mutation in hui and han people.
Methods By using polymerase chain reaction and direct DNA sequencing , BRCA1 mutations were detected in 130 women breast cancer cases and 80 cases of healthy people (Including 30 cases of Hui people and 50 cases of Han people).Statistical treatment of experimental data using statistical packages SPSS13.0 using chi-square test and Fisher's exact test. Immunohistochemistry in the hierarchy of information using Mann-Whitney test, the factors associated with the BRCA1 breast cancer gene mutations using Logistic regression statistics. In order to test the level ofα= 0.05.
Results (1)15 loci of BRCA1 gene mutation were detected in 130 case of women breast cancer patients, four cases of mutations in breast cancer information center website BIC (Breast Cancer Information Core)have reported, two cases of exon 11 2201C> T mutation, 1 case of 2548del A in exon 11, 1 case of exon 11 2754 G> A, 11 case BRCA1 gene mutation have not been reported at home and abroad, were 1 case of missense mutation (139G> T)in the exon2, one case missense mutation(5317A> T) in exon 20, 5 cases of missense mutation(respectively, 2403 A> G, 2405A> T, 943 G> A, 981A> G, 984 A> T) in exon 11, 4 cases exon 11 shift mutation (respectively, 2722delC, 3126insT, 944delC, 944delC) (2) The frequency of BRCA1 mutation in 130 women breast cancer cases was 11.54 %(15/ 130) . Among them there are 12 gene mutations in the 90 cases of breast cancer of Han people,the rate is 13.33%(12/90), 40 cases of breast cancer, there are three cases of gene mutation in hui people, the gene mutation rate was 7.5%(3/40), Han breast cancer gene mutation rate was 13.33%(12/90) ,higher than the Hui breast cancer gene mutation rate of 7.5% (3/40), between the BRCA1 breast cancer gene mutation rate there is no significant difference (χ2= 0.923, P >0.05) ;(3) The frequency of BRCA1 mutation in women early onset breast cancer was 20.4% (10/49) , which was higher than that in late onset group (5/81 ,6.2%)(χ2 =6.061 , P < 0. 05) (4)The frequency of estrogen receptor、progesterone receptor and human epidermal growth factor receptor negative(called triple-negative breast cancer) of BRCA1 mutation was 66.7%(10/15),which was higher than non-BRCA1 mutation related breast cancer was 25.2%(29/115)(χ2 =10.852 , P < 0.05);(5)BRCA1 gene mutation-related breast cancer lymph node metastasis rate was 93.33%(14/15), higher than the non BRCA1-related breast cancer gene mutation 61.74%(71/115)(χ2 =5.852,P<0.05).
Conclusion (1) BRCA1 gene mutation related with breast cancer;(2) BRCA1 breast cancer gene mutations showed no significant difference between Ningxia Hui and Han people;(3) This study we found mutations BRCA1 gene in 15 cases, 4 cases are consistent with the existing literature while 10 mutations in 11 cases of breast cancer cases were first found, also not found "ancestor mutation" in the Chinese population; (4) Compared to the non-mutation group BRCA1 gene mutation in breast cancer has the high proportion of histological grade III and ER、PR、CerbB-2 negative increased trend, showing that BRCA1 gene mutation is related with immunohistochemical characteristics ;(5) early-onset breast cancer is related with BRCA1 gene mutation; (6) BRCA1 gene mutation more likely to lymph node metastasis, and prompted poor prognosis.
方法(1)样本来源:收集宁夏地区乳腺癌患者全血标本130例(回族40例,汉族90例),对照组80例(汉族50例,回族30例)。回族要求三代保留其民族遗传、地域、风俗、文化和生活背景;(2)实验方法:本课题采用PCR直接测序法(PCR:Polymerase Chain Reaction聚合酶链反应)检测汉族、回族及同一地区无肿瘤病史的正常对照者的BRCA1基因突变情况;(3)实验数据统计处理运用SPSS13.0统计软件包,其中率的检验采用卡方检验。免疫组化结果分析采用Mann-Whitney检验,各因素与BRCA1基因突变相关性乳腺癌统计采用非条件Logistic回归。以α=0.05为检验水准。
结果(1) 130例乳腺癌中共发现15例BRCA1基因突变,4例突变在乳腺癌信息中心网站BIC(Breast Cancer Information Core)有报道,2例11号外显子2201C> T突变,1例11号外显子2548del A,1例11号外显子2754 G>A ,11例BRCA1基因碱基突变国内外未见报道,分别为2号外显子的错义突变1例(139G>T),20号外显子的错义突变1例(5317A> T),11号外显子错义突变5例(分别为2403 A> G,2405A>T,943 G>A,981A>G,984 A>T),11号外显子移码突变4例(分别为2722delC,3126insT,944delC,944delC);(2) 130例乳腺癌BRCA1外显子总的突变率为11.54% (15/130),其中90例汉族乳腺癌中有12例发生突变,基因突变率13.33%(12/90),40例回族乳腺癌中有3例发生突变,基因突变率为7.5%(3/40),汉族乳腺癌基因突变率为13.33%(12/90)高于回族乳腺癌基因突变率7.5%(3/40),两者相比经统计学分析无显著性差异(χ2=0.923,P>0.05);(3)130例回、汉族乳腺癌患者中,49例早发性乳腺癌(≤35岁) BRCA1基因突变率为20.4%(10/49)。早发性乳腺癌BRCA1基因突变率(10/ 49)高于晚发性乳腺癌BRCA1基因突变率6.2%(5/81) ,差异有统计学意义(χ2 =6.061 , P < 0. 05) ;(4)15例BRCA1基因突变的乳腺癌中有10例为ER(雌激素受体)阴性、PR(孕激素受体)阴性、人表皮生长因子受体2(HER-2)阴性,即三阴乳腺癌,其比例为66.7%(10/15),而非BRCA1基因突变的乳腺癌中三阴比例为25.2%(29/115),经统计学分析有显著性差异(χ2=10.852 , P < 0.05) ;(5)BRCA1基因突变相关性乳腺癌淋巴结转移率为93.33%(14/15),高于非BRCA1基因突变相关性乳腺癌61.74%(71/115),差异有统计学意义(χ2 =5.852,P<0.05 )。
结论(1)BRCA1基因突变与乳腺癌有密切关系;(2)宁夏地区回、汉族乳腺癌BRCA1基因突变率无明显差异;(3)本研究发现15例突变,其中4例与已有的文献报道一致,11例乳腺癌的10种突变位点均为首次发现,未发现中国人群的“始祖突变”;(4)BRCA1基因突变相关性乳腺癌与非突变对照组相比,具有肿瘤组织学分级III级比例高,ER、PR、CerbB-2阴性率增高的趋势,提示BRCA1基因突变与免疫组化特点存在相关;(5)早发性乳腺癌的发生与BRCA1基因突变有关;(6)BRCA1基因突变相关性乳腺癌更容易发生淋巴结转移,且提示预后较差。
Objective To analyze the mutations of BRCA1 in breast cancer patients in Ningxia. BRCA1 is a hereditary breast and ovarian cancer susceptibility gene (hereditary breast and ovarian cancer susceptibility gene), this experimental study breast cancer patient BRCA1 gene mutation situation and the mutation site of hui and han people in Ningxia.Discuss the relationship between BRCA1 gene mutation and breast cancer, simultaneously analyze the breast cancer BRCA1 gene mutation in hui and han people.
Methods By using polymerase chain reaction and direct DNA sequencing , BRCA1 mutations were detected in 130 women breast cancer cases and 80 cases of healthy people (Including 30 cases of Hui people and 50 cases of Han people).Statistical treatment of experimental data using statistical packages SPSS13.0 using chi-square test and Fisher's exact test. Immunohistochemistry in the hierarchy of information using Mann-Whitney test, the factors associated with the BRCA1 breast cancer gene mutations using Logistic regression statistics. In order to test the level ofα= 0.05.
Results (1)15 loci of BRCA1 gene mutation were detected in 130 case of women breast cancer patients, four cases of mutations in breast cancer information center website BIC (Breast Cancer Information Core)have reported, two cases of exon 11 2201C> T mutation, 1 case of 2548del A in exon 11, 1 case of exon 11 2754 G> A, 11 case BRCA1 gene mutation have not been reported at home and abroad, were 1 case of missense mutation (139G> T)in the exon2, one case missense mutation(5317A> T) in exon 20, 5 cases of missense mutation(respectively, 2403 A> G, 2405A> T, 943 G> A, 981A> G, 984 A> T) in exon 11, 4 cases exon 11 shift mutation (respectively, 2722delC, 3126insT, 944delC, 944delC) (2) The frequency of BRCA1 mutation in 130 women breast cancer cases was 11.54 %(15/ 130) . Among them there are 12 gene mutations in the 90 cases of breast cancer of Han people,the rate is 13.33%(12/90), 40 cases of breast cancer, there are three cases of gene mutation in hui people, the gene mutation rate was 7.5%(3/40), Han breast cancer gene mutation rate was 13.33%(12/90) ,higher than the Hui breast cancer gene mutation rate of 7.5% (3/40), between the BRCA1 breast cancer gene mutation rate there is no significant difference (χ2= 0.923, P >0.05) ;(3) The frequency of BRCA1 mutation in women early onset breast cancer was 20.4% (10/49) , which was higher than that in late onset group (5/81 ,6.2%)(χ2 =6.061 , P < 0. 05) (4)The frequency of estrogen receptor、progesterone receptor and human epidermal growth factor receptor negative(called triple-negative breast cancer) of BRCA1 mutation was 66.7%(10/15),which was higher than non-BRCA1 mutation related breast cancer was 25.2%(29/115)(χ2 =10.852 , P < 0.05);(5)BRCA1 gene mutation-related breast cancer lymph node metastasis rate was 93.33%(14/15), higher than the non BRCA1-related breast cancer gene mutation 61.74%(71/115)(χ2 =5.852,P<0.05).
Conclusion (1) BRCA1 gene mutation related with breast cancer;(2) BRCA1 breast cancer gene mutations showed no significant difference between Ningxia Hui and Han people;(3) This study we found mutations BRCA1 gene in 15 cases, 4 cases are consistent with the existing literature while 10 mutations in 11 cases of breast cancer cases were first found, also not found "ancestor mutation" in the Chinese population; (4) Compared to the non-mutation group BRCA1 gene mutation in breast cancer has the high proportion of histological grade III and ER、PR、CerbB-2 negative increased trend, showing that BRCA1 gene mutation is related with immunohistochemical characteristics ;(5) early-onset breast cancer is related with BRCA1 gene mutation; (6) BRCA1 gene mutation more likely to lymph node metastasis, and prompted poor prognosis.
引文
[1] Burke W, Daly M, Garber J, et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer[J]. JAMA 1997;277: 997–1003.
[2] Sakorafas GH. The management of women at high risk for the development of breast cancer: risk estimation and preventative strategies. Cancer Treat Rev 2003: 29: 79–89.
[3] Miki Y,Swensen J,Shattuck -Eidens D,et al.A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1[J].Science,1994,266: 66-71.
[4] Irminger - Finger I, Siegel BD, Leung WC. The functions of breast cancer susceptibility gene 1 (BRCA1) product and its associated proteins[J]. Biol Chem,1999,380(2): 117-128.
[5] Sakorafas GH, Tsiotou AG. Genetic predisposition to breast cancer:a surgical perspective[J]. Br J Surg,2000, 87(2): 149-162.
[6] Kauff ND, Satogopan JM, Robson ME, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. New Engl [J]Med 2002;346: 1609–1512.
[7] Wittliff JL.Steroid-Hormone receptors in breast cancer[J].Cancer,1984,53: 630
[8] Helin HJ,et al.Immunohistochemical determination of estrogen and progesterone receptors in human breast carcinoma.Cancer,1989,63-761
[9]许良中,许世明,刘亦法等.101例乳腺癌雌激素受体测定[J].肿瘤,1984,14: 18.
[10] Evaluation of the United States Food and Drug Administration-approved Scoring and Test System of HER-2 Protein Expression in Breast Cancer[J].Clinical Cancer Research,1669,2001,7,1669-1675.
[11] Jacobs TW, Gown AM,Yaziji H, BarnesMJ, et al. Specificity of HercepTest in Determining HER-2/neu Status of Breast Cancers Using the United States Food and Drug Administration Approved Scoring System[J]. Journal of Clinical Oncology, 1999, 17 (7) : 1983-1987.
[12] Black DM,Nicolai H,BorrowJ,et al.A somatic cell hybrid map of the long arm of humanchromosome17,containing the familial breast cancer locus (BRCA1) [J].Am J Hum Genet,1993: 52(4): 702-710.
[13] Liaw D,Marsh D,LI J,et al.Germline mutation of PTEN gene in Cowden disease,an inherited breast and thyroid cancer syndrome[J].Nature Genet,1997,(16): 64-67.
[14] Infante M, Duran M, Acedo A, et al.BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin[J]. Clin Genet, 2009,(14): 32-34.
[15] Ford D,Easton DF,St ratton M,et al.Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families.The Breast Cancer Linkage Consortium.Am J Hum Genet,1998,62(3): 676-689.
[16] By C.T.M. Brekelmans, C. Seynaeve, C.C.M. Bartels, et al. Effectiveness of Breast Cancer Surveillance in BRCA1/2 Gene Mutation Carriers and Women With High Familial Risk[J]. Journal of Clinical Oncology, 2001 Vol (19)924-930.
[17] Monika K. Graeser, Christoph Engel, Kerstin Rhiem,et al. Contralateral Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers[J]. Journal of Clinical Oncology, 2009 Vol (27)5887-5892.
[18] Rie I,Takashi F,Toshikazu U,et al.Germline mutation of BRCA1 in Japanese breast cancer families[J].Cancer Res,1995,55: 3521~3524.
[19]史玉荣,李臣宾,只向成等.家族性乳腺癌易感基因-1突变的研究.中华实验外科杂志[J],2005,22(10): 1269.
[18]胡震,沈镇宙,邵志敏,等.中国家族性和早发性乳腺癌BRCA1基因突变的研究[J].中华肿瘤杂志,2004,26(11): 657-659.
[21] Friedman LS,Szabo CI,Ostermeyer EA,et al.Novel inheri ted mutations and variable expressivity of BRCA1 alleles,including the founder mutation 185delAG in Ash-kenaziJewish families[J].Am J Hum Genet,1995,57: 1284-1297.
[22]王曦,杨名添,方嬿,等.231例乳腺癌患者乳腺癌易感基因BRCA1的突变检测及分析[J].癌症, 2001,20(9): 916-920.
[23]马怡红,付坚,吴秉铨.53例家族性乳腺癌BRCA1和BRCA2基因部分序列的突变分析[J].北京医科大学学报, 2000,32(1): 86-88.
[24]张海添,陆云飞.散发性乳腺癌BRCA1、BRCA2基因突变研究[D].博士学位论文, 2006年5月.
[25]Shattuck EidensD,OliphantA,Mcclure M,et al. [J]美国医学杂志中文版,1998,17(5): 226-233.
[26] FitzGerald MG, MacDonald DJ,Krainer M, et al. Germ-line brca1 mutations in Jewish and non-Jewish women with early-onset breast cancer[J].New England med, 1996,334(3): 143-149.
[27]付欣鸽,李锋,王振华等.维吾尔族及汉族乳腺癌BRCA1基因突变检测及分析[J].现代预防医学, 2007, 34(9):1612-1615.
[28] NoguehiS,Kasugai,TMiki,Y et al.Clinic Pathologic analysis of BRCA1-Or BRCA2-associated hereditary breast carcinoma in Japanese women[J].Cancer,1999, 85(10): 2200-2205.
[29] Amres JE,TruteL,WhiteD,et al:Distinct molecular Pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers:A population-based study.Cancer Res,1999,59(8):2011-2017.
[30] Lynch BJ,Holden JA,Buys SS,et al:Pathobiologic characteristics of hereditary breast cancer.Hum Pathol,1998,29(10):1140-1144.
[31] Lakhani SR,van de Vijver MJ,Jacquemier J,et al.The pathology of familial breast cancer:predictive value of immunohistochemical markers estrogen receptor,progesterone receptor,HER-2,and P53 in patients with mutations in BRCA1 and BRCA2[J].Clin Oncol,2002,20: 2310-2318.
[32] Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours [J]. Nature, 2000, 406 (6797): 447-752.
[33] Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications [J]. Proc Natl Acad Sci USA, 2001, 98 (69): 10869-10874.
[34] Sorlie T. Molecular portraits of breast cancer: Tumor subtypes as distinct disease entities [J]. Eur J Cancer, 2004, 40(18): 2667-2675.
[35] Brenton JD, Carey LA, Ahmed AA, et al. Molecular classification and molecular forecasting of breast cancer: Ready for clinical application[J]. J Clin Oncol, 2005, 23(29): 7350-7360.
[36] Sotiriou C, Neo SY, McShane LM, et al. Breast cancer classification and prognosis based on gene expression profiles from a population-based study[J]. Proc Natl Acad Sci USA, 2003, 100 (18): 10393-10398.
[37] Lidereau R,Eisinger F,Champeme MH,et al.Major improvement in the efficacy of BRCA1 mutation screening using morphoclinical features of breast cancer[J].Cancer Res,2000;60(5): 1206-1210.
[38] Chang J,Hilsenbeck SG Sng JH,et al.Pathological Features and BRCA1 Mutation Sereening in Premenopausal Breast Cancer Patients[J].Clinical Caneer Research, 2001;7(6): 1739-1742.
[1] Easton DF,Ford DT. Breast and ovarian cacer incidence in BRCA-mutation carries.Breast Cancer Linkage Consortium[J].Am Hum Genet, 1995,56(1):265-271.
[2] Mcinerney Leo A,Hadley D,Kase RG,et al.BRCA1/2 testing in hereditary breast and ovarian cancer familiesⅢ:Risk perception and screening.Am J Med Genet A [J],2006,140(20):2198-206.
[3] Hall JK,Lee MK,Newman B,et al.Linkage of early onset familial breast cancer to chromosome17q21[J].Science,1990,250:1684-1689
[4] Zheng L,Li S,Boyer TG,et al.Lessons learned from BRCA1 and BRCA2[J]. Oncogene,2000,19:6159-6175.
[5] Shiozaki EN,Gu L,Yan N,et al.Structure of the BRCT repeats of BRCA1 bound toa BACH1 phosphopeptide:im-plications for signaling[J].Mol Cell,2004,14(3):405-410.
[6]许奕.BRCA1的研究进展[M].北京医学,2005,27(1):50-52.
[7] Kubissta M,Rosner M,Kubista E,et al. BRCAl regulates in vitro differentiation of mammary epithelial cells[J].Oncogene,2002,21(31):2173-2178.
[8] Pan S,Yuan R,Ma YX,et al. BRCA1 genes antagonize phenotype of wild-type BRCA1[J]. Oncogene,2001,20(57): 8215-8235.
[9] Haile DT,Parvin JD.Activation of transcription in vitro by the BRCA1 carboxyl- terminal domain[J].Biol Chem,1999,274: 2113-2117.
[10] Wang H,BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1b are tyrosine phosphor-proteins that associate with E2F,cyclins and cyclin dependent kinase[J].Oncogene,1997,15(2):143-157.
[11] Hsu LC,Doan TP,White RL.Identification of a gamma-tubulin-binding domain in BRCA1[J].Cancer Res,2001,61(21):7713-7718.
[12] Tan W,Zheng L,Lee WH,et al.Functional dissection of transcription factor ZBRK1 reveals zine fingers with dualroles in DNA-binding and BRCA1-dependenttranscriptional repression[J].Biol Chem,2004,279(8): 6576-6587.
[13] Paul TT,Cortez D,Browse B,et al.Direct DNA binding by Brca1[J].Proc Natl AcadSci U S A,2001,98(11):6086-6091.
[14]Hashizume R,Fukuda M,Maeda I,et al.The RING het-erodimer BRCA1-BARD1 is an ubiquitin ligase inactivated by a breast cancer-derived mutation[J]. Biol Chem,2001,276(18): 14537-14540.
[15] Westermark UK,Reyngold M,Olshen AB,et al.BARD1 participates with BRCA1 inhomology-directed repair of chromosome breaks[J].Mol Cell Biol,2003,23(21): 926-936.
[16] Khanna KK,Jackson SP.DNA double stand breaks signal-ing,repair and the cancer connection[J].Nat Genet,2001,27(3): 247-254.
[17] Zhang J,Wilers H,Feng Z,et al.Chk2 phosphorylation of BRCA1 regulates DNA double-strand break repair[J].Mol Cell Biol,2004,24(2): 708-713.
[18] Cantor, Haber, D. A. and Livingston, D. M.et al[J]. BACH1, a novel helicase- like protein, interacts directly with BRCA1 and contributes to its DNA repair function[J]. Cell,2001,1(5): 149-160.
[19] MaLachlan TK,Takimoto R,El-Deiry WS.BRCA1 directs a selective P53-dependenttranscriptional response towards growth arrest and DNA repair targets[J].Mol CellBiol,2002,22(12): 4280-4292.
[20] Arizti P, Fang L, Park I, et al.Tumor suppressor P53 is required to modulate BRCA1 expression[J].Mol Cell Biol,2000,20(20): 7450-7459.
[21] Somasundaram.Arrest of cell cycle by the tumor-suppressor BRCA1 requires the CDK-inhibitor P21WAF1/CiP1[J].Nature,1997,389(6647): 187-190.
[22] Fan W,Jin S,Tong .BRCA1 regulates GADD45 through its interactions with the OCT-1 and CAAT motifs[J].J Biol Chem,2002,277(10): 8061-8067.
[23] Williamson EA,Dadmanesh F,Koeffler HP.BRCA1 transactivates the cyclin-dependent kinase inhibitor P27(Kip1)[J].Oncogene,2002,277(20): 3199-3206.
[24] Zhou C,Liu J.Inhibition of human telomerase reverse transcriptase gene expressionby BRCA1 in human ovarian cancer cells[J].Biochem Biophys Res Commun, 2003 ,303 (1): 30-136.
[25] Fan S,Yuan R,Ma YX,et al.Mutant BRCA1 genes an-tagonize phenotype of wild-type BRCA1[J].Oncogene,2001,20(57): 8215-8235.
[26] Harkin DP,Bean JM.Induction of GADD45 and JNK/SAPK dependent apoptosis following inducible expression of BRCA1[J].Cell,1999,97(5): 575-586.
[27] Yan Y,Haas JP,Kim M,et al.BRCA1-induced apoptosis involves inactivation of ERK1/2 activities[J].Biol Chem,2002,277(36):33422-33430.
[28] Hsu LC,Doan TP,White RL.Identification of a gamma-tubulin-binding domain in BRCA1[J].Cancer Res,2001,61(21): 7713-7718.
[29] Niamh E. Buckley, Alison M. Hosey, Julia J. Gorski, et al BRCA1 Regulates IFN;Signaling through a Mechanism Involving the Type I IFN[J],Mol Cancer Res 2007,5(3): 261–70.
[30] FitzGerald MG, MacDonald DJ,Krainer M, et al. Germ-line brca1 mutations in Jewish and non-Jewish women with early-onset breast cancer[J].New England J med,1996,334(3): 143-149.
[31] Inoue R,Fukutomi T, Ushijima T, et al. Germline mutation of BRCA1 in Japanese breast cancer families [J].Cancer Res,1995,55(16): 3521-3524.
[32] Thompson ME,Jensen RA, Obermiller PS,et al.Decreased expression of BRCA1 accelerates growth and is often present during sporadic breast cancer progression [J].Nat Genet,1995,9 (4): 444-450.
[33]赖春宁,江泽飞,宋三泰,等.186例乳腺癌患者BRCA1基因突变检测[J].中华肿瘤杂志,2001, 23(6): 483-485
[34] Hall JM,Lee MK,Newman B,et al.Linkage of early-onset familial breast cancer tochromosome 17q21[J].Science, 1990, 250(4988): 1684-1689.
[35] Narod SA, Feunteun J,Lynch HT,et al.Familial breast-ovarian cancer locus on chromosome 17q12-q23[J]. Lancet,1991,338(8759): 82-83.
[36] Hall JM, Friedman L, Guenther C.Closing in on a breast cancer gene on chromosome 17q[J]. Am Hum Genet,1992,50(6): 1235-1242.
[37] Easton DF,Bishop DT,Ford P,et al.Genetic linkage analysis in familial breast and ovarian cancer:Results from 214 families[J].Am J Hum Genet,1993,52(4): 678-701
[38] Easton DF,Ford D,Bishop DT,et al.Breast and ovarian cancer incidence in BRCA1mutation carriers[J].Am Hum Genet,1995,56(1): 265-271.
[39] Easton DF,Narod SA,Ford D,et al.The genetic epidemiology of BRCA1[J].Lancet, 1994,344(8924): 761.
[40] Ford D,Easton DF,Bishop DT,et al.Risk of cancer in BRCA1 mutation carrier[J]. Lancet,1994,343(8899): 692-695.
[41] Goldgar DF, Fields P,Lewis CM,et al.A large kindred with 17q-linked breast and ovarian cancer:Genetic phenotypic and genealogical analysis[J].Natl Cancer Inst, 1994,86(3): 200-209.
[42]甄林林,武正炎,范萍等.家族性乳腺癌乳腺癌易感基因-1突变分析[J].中华实验外科杂志,2003,20(2): 170-171.
[43] Yang Hong, Zhou Lei-lei,Liu Jin-ping,et al.Relation ship between the expression of the BRCA1 protein and clinicopathological characteristics of breast cancer[J]. China oncology, 2003,13(1):13-16.
[44]易韦,文安智. BRCA1在散发性乳腺浸润性导管癌癌组织中的表达及意义[J].山东医药, 2008,48(26): 82-83.
[45] Crook T,Crossland S,Crompton M R,Osin P,Gusterson B A.P53 mutations in BRCA1-associated breast cancer[J]. Lancet, 1997,350: 638-639.
[46] Somasundaram K,Zhang H,et al.Arrest of the cell cycle by the tumour suppress-or BRCA1 requires the CDK-in-hibitor P21Waf1/Cip1[J].Nature(Lond),1997,389: 187-190.
[47] Zhang H, Somasundaram K, et al.BRCA1 physically associates with P53 and stim-ulates its transcriptional activity[J]. Oncogene, 1998,16:1713-1721.
[48] Arizti P, Fang L,Park I,et al.Tumor suppressor P53 is required to modulate BRCA1 expression[J]. Mol Cell Biol,2000, 20(20): 7450-7459.
[49] Stoppa-Lyonnet D,Ansquer Y,Dreyfus et al.Familial invasive breast cancer: worse outcome related to BRCA1 mutations[J].Clin Oncol,2000,18(24): 4053-4059.
[50] Kennedy R D,Quinn J E,Mullan P B,et al.The role of BRCA1 in the cellular response to chemotherapy[J].J Natl Cancer Inst,2004,96(22): 1659-1668.
[51] Haffty B G,Yang Q F,Reiss M,et al.Locoregional Relapse and Distant Metastasis in Conservatively Managed Triple Negative Early-Stage Breast Cancer[J]. Clin Oncol,2006,24(36): 5652-5657.
[52] Rodriguez-Pinilla S M,Sarrio D,Honrado E,et al.Prognostic signifficance of basal-like phenotype and fascin expression in node negative invasive breast carcinomas[J].Clin Cancer Res,2006,12(5): 1533-1539.
[53]袁中玉,王树森,高岩,等.305例三阴乳腺癌患者的临床特征及预后因素分析[J].癌症, 2008,27(6): 561-565.
[54] Minn A J,Gupta G P,Siegel P M,et al.Genes that mediate breast cancer metastasisto lung[J].Nature,2005,436(7050): 518-524.
[55] Carey L A, Perou C M, Livasy C A,et al.Race,breast cancer subtypes,and survivalin the Carolina Breast Cancer Study[J]. JAMA,2006,295(21): 2492-2502.
[56] Hoadley KA, Weigman VJ, Fan C, et al.EGFR associated expression profiles vary with breast tumor subtype[J]. BMC Genomics 2007(8): 258–276.
[57] Siziopikou KP, Ariga R, Proussaloglou KE, et al. The challenging estrogen receptor-negative/progesterone receptor-negative/Her-2-negative patient: a promisingcandidate for epidermal growth factor receptor-targeted therapy[J]. Breast 2006(12): 360–362.
[58] Siziopikou KP, Cobleigh M.The basal subtype of breast carcinomas may representthe group of breast tumors that could benefit from EGFR-targeted therapies.Breast2007(16): 104–107.
[59] Miki Y,Swensen J,Shattuck-Eidens D,et al.A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1[J].Science,1994,266(7): 66-71.
[60] Rie I,Takashi F,Toshikazu U,et al.Germline mutation of BRCA1 in Japanese breast cancer families[J].Cancer Res,1995,55: 3521-3524
[61]史玉荣,李臣宾,只向成等.家族性乳腺癌易感基因-1突变的研究[J].中华实验外科杂志,2005,22(10): 1269
[62]胡震,沈镇宙,邵志敏,等.中国家族性和早发性乳腺癌BRCA1基因突变的研究[J].中华肿瘤杂志,2004,26(11): 657-659.
[63] Friedman LS,Szabo CI,Ostermeyer EA,et al.Novel inheri ted mutations and variable expressivity of BRCA1 alleles,including the founder mutation 185delAG in AshkenaziJewish families[J].Am Hum Genet,1995,57: 1284-1297.
[64]王曦,杨名添,方嬿,等.231例乳腺癌患者乳腺癌易感基因BRCA1的突变检测及分析[J].癌症,2001,20(9): 916-920
[65]马怡红,付坚,吴秉铨.53例家族性乳腺癌BRCA1和BRCA2基因部分序列的突变分析[J].北京医科大学学报,2000,32(1): 86
[66] Miki Y,Swensen J,Shattuck-Eidens D,et al.A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1[J].Science,1994,266(7): 66-71.
[67] Shattuck-Eidens D,McClure M,Simard J,et al.A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene[J].JAMA,1995,273(7)∶535-541.
[68] Futreal PA,Liu Q,Shattuck-Eidens D,et al.BRCA1 mutions in primary breast andovarian carcinomas[J].Science,1994,266(7): 120-122.
[69] Takahashi H, Behbakht K,McGovern PE,et al.Mutation analysis of the BRCA1 gene in ovarian cancers[J].Cancer Res,1995,55(14): 2998-3002.
[70] Struewing JP,Brody LC,Erdos MR,et al.Detection of eight BRCA1 mutations in 10breast/ovarian cancer families,including 1 family with male breast cancer[J].Am Hum Genet,1995,57(1): 1-7.
[71] Muto MG,Gramer DW,Tangir J,et al.Frequency of the BRCA1 185 delAG mutation among Jewish women with ovarian cancer and matched population controls[J].Cancer Res,1996,56(6): 1250-1252.
[72] Johnson ,Ostermetyer EA,HaKasson S,et al.Founding BRCA1 mutations in hereditary breast and ovarian cancer in southern Sweden[J].Am J Hum Genet,1996,58(3): 441-450.
[73] Foulkes WD,Stefansson IM,Chappuis PO,et al.Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer[J].Natl Cancer Inst,2003,95(19): 1482-1485.
[74] DaveG,Cosmatos H, Do T,et al.Metaplastic carcinoma of the breast ;A retrospective review[J].Int Radiat oncol Biol Phys,2006,64(3): 771-775.
[75] Kauff ND,Brogi.Epithelial lesions in prophylactic mastectomy specimens from women with BRCA mutations[J].Cancer,2003,97(7): 1601-1608.
[76] Esteva FJ, Sahin AA, Cristofanilli M, et al. Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy[J].Clinic Cancer Res. 2005,(11): 315-319.
[77] Ma XJ, Salunga R, Tuggle JT, et al. Gene expression profiles of human breast cancer progression[J]. Proc Natl Acad Sci USA. 2000, (59): 74-79.
[2] Sakorafas GH. The management of women at high risk for the development of breast cancer: risk estimation and preventative strategies. Cancer Treat Rev 2003: 29: 79–89.
[3] Miki Y,Swensen J,Shattuck -Eidens D,et al.A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1[J].Science,1994,266: 66-71.
[4] Irminger - Finger I, Siegel BD, Leung WC. The functions of breast cancer susceptibility gene 1 (BRCA1) product and its associated proteins[J]. Biol Chem,1999,380(2): 117-128.
[5] Sakorafas GH, Tsiotou AG. Genetic predisposition to breast cancer:a surgical perspective[J]. Br J Surg,2000, 87(2): 149-162.
[6] Kauff ND, Satogopan JM, Robson ME, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. New Engl [J]Med 2002;346: 1609–1512.
[7] Wittliff JL.Steroid-Hormone receptors in breast cancer[J].Cancer,1984,53: 630
[8] Helin HJ,et al.Immunohistochemical determination of estrogen and progesterone receptors in human breast carcinoma.Cancer,1989,63-761
[9]许良中,许世明,刘亦法等.101例乳腺癌雌激素受体测定[J].肿瘤,1984,14: 18.
[10] Evaluation of the United States Food and Drug Administration-approved Scoring and Test System of HER-2 Protein Expression in Breast Cancer[J].Clinical Cancer Research,1669,2001,7,1669-1675.
[11] Jacobs TW, Gown AM,Yaziji H, BarnesMJ, et al. Specificity of HercepTest in Determining HER-2/neu Status of Breast Cancers Using the United States Food and Drug Administration Approved Scoring System[J]. Journal of Clinical Oncology, 1999, 17 (7) : 1983-1987.
[12] Black DM,Nicolai H,BorrowJ,et al.A somatic cell hybrid map of the long arm of humanchromosome17,containing the familial breast cancer locus (BRCA1) [J].Am J Hum Genet,1993: 52(4): 702-710.
[13] Liaw D,Marsh D,LI J,et al.Germline mutation of PTEN gene in Cowden disease,an inherited breast and thyroid cancer syndrome[J].Nature Genet,1997,(16): 64-67.
[14] Infante M, Duran M, Acedo A, et al.BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin[J]. Clin Genet, 2009,(14): 32-34.
[15] Ford D,Easton DF,St ratton M,et al.Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families.The Breast Cancer Linkage Consortium.Am J Hum Genet,1998,62(3): 676-689.
[16] By C.T.M. Brekelmans, C. Seynaeve, C.C.M. Bartels, et al. Effectiveness of Breast Cancer Surveillance in BRCA1/2 Gene Mutation Carriers and Women With High Familial Risk[J]. Journal of Clinical Oncology, 2001 Vol (19)924-930.
[17] Monika K. Graeser, Christoph Engel, Kerstin Rhiem,et al. Contralateral Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers[J]. Journal of Clinical Oncology, 2009 Vol (27)5887-5892.
[18] Rie I,Takashi F,Toshikazu U,et al.Germline mutation of BRCA1 in Japanese breast cancer families[J].Cancer Res,1995,55: 3521~3524.
[19]史玉荣,李臣宾,只向成等.家族性乳腺癌易感基因-1突变的研究.中华实验外科杂志[J],2005,22(10): 1269.
[18]胡震,沈镇宙,邵志敏,等.中国家族性和早发性乳腺癌BRCA1基因突变的研究[J].中华肿瘤杂志,2004,26(11): 657-659.
[21] Friedman LS,Szabo CI,Ostermeyer EA,et al.Novel inheri ted mutations and variable expressivity of BRCA1 alleles,including the founder mutation 185delAG in Ash-kenaziJewish families[J].Am J Hum Genet,1995,57: 1284-1297.
[22]王曦,杨名添,方嬿,等.231例乳腺癌患者乳腺癌易感基因BRCA1的突变检测及分析[J].癌症, 2001,20(9): 916-920.
[23]马怡红,付坚,吴秉铨.53例家族性乳腺癌BRCA1和BRCA2基因部分序列的突变分析[J].北京医科大学学报, 2000,32(1): 86-88.
[24]张海添,陆云飞.散发性乳腺癌BRCA1、BRCA2基因突变研究[D].博士学位论文, 2006年5月.
[25]Shattuck EidensD,OliphantA,Mcclure M,et al. [J]美国医学杂志中文版,1998,17(5): 226-233.
[26] FitzGerald MG, MacDonald DJ,Krainer M, et al. Germ-line brca1 mutations in Jewish and non-Jewish women with early-onset breast cancer[J].New England med, 1996,334(3): 143-149.
[27]付欣鸽,李锋,王振华等.维吾尔族及汉族乳腺癌BRCA1基因突变检测及分析[J].现代预防医学, 2007, 34(9):1612-1615.
[28] NoguehiS,Kasugai,TMiki,Y et al.Clinic Pathologic analysis of BRCA1-Or BRCA2-associated hereditary breast carcinoma in Japanese women[J].Cancer,1999, 85(10): 2200-2205.
[29] Amres JE,TruteL,WhiteD,et al:Distinct molecular Pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers:A population-based study.Cancer Res,1999,59(8):2011-2017.
[30] Lynch BJ,Holden JA,Buys SS,et al:Pathobiologic characteristics of hereditary breast cancer.Hum Pathol,1998,29(10):1140-1144.
[31] Lakhani SR,van de Vijver MJ,Jacquemier J,et al.The pathology of familial breast cancer:predictive value of immunohistochemical markers estrogen receptor,progesterone receptor,HER-2,and P53 in patients with mutations in BRCA1 and BRCA2[J].Clin Oncol,2002,20: 2310-2318.
[32] Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours [J]. Nature, 2000, 406 (6797): 447-752.
[33] Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications [J]. Proc Natl Acad Sci USA, 2001, 98 (69): 10869-10874.
[34] Sorlie T. Molecular portraits of breast cancer: Tumor subtypes as distinct disease entities [J]. Eur J Cancer, 2004, 40(18): 2667-2675.
[35] Brenton JD, Carey LA, Ahmed AA, et al. Molecular classification and molecular forecasting of breast cancer: Ready for clinical application[J]. J Clin Oncol, 2005, 23(29): 7350-7360.
[36] Sotiriou C, Neo SY, McShane LM, et al. Breast cancer classification and prognosis based on gene expression profiles from a population-based study[J]. Proc Natl Acad Sci USA, 2003, 100 (18): 10393-10398.
[37] Lidereau R,Eisinger F,Champeme MH,et al.Major improvement in the efficacy of BRCA1 mutation screening using morphoclinical features of breast cancer[J].Cancer Res,2000;60(5): 1206-1210.
[38] Chang J,Hilsenbeck SG Sng JH,et al.Pathological Features and BRCA1 Mutation Sereening in Premenopausal Breast Cancer Patients[J].Clinical Caneer Research, 2001;7(6): 1739-1742.
[1] Easton DF,Ford DT. Breast and ovarian cacer incidence in BRCA-mutation carries.Breast Cancer Linkage Consortium[J].Am Hum Genet, 1995,56(1):265-271.
[2] Mcinerney Leo A,Hadley D,Kase RG,et al.BRCA1/2 testing in hereditary breast and ovarian cancer familiesⅢ:Risk perception and screening.Am J Med Genet A [J],2006,140(20):2198-206.
[3] Hall JK,Lee MK,Newman B,et al.Linkage of early onset familial breast cancer to chromosome17q21[J].Science,1990,250:1684-1689
[4] Zheng L,Li S,Boyer TG,et al.Lessons learned from BRCA1 and BRCA2[J]. Oncogene,2000,19:6159-6175.
[5] Shiozaki EN,Gu L,Yan N,et al.Structure of the BRCT repeats of BRCA1 bound toa BACH1 phosphopeptide:im-plications for signaling[J].Mol Cell,2004,14(3):405-410.
[6]许奕.BRCA1的研究进展[M].北京医学,2005,27(1):50-52.
[7] Kubissta M,Rosner M,Kubista E,et al. BRCAl regulates in vitro differentiation of mammary epithelial cells[J].Oncogene,2002,21(31):2173-2178.
[8] Pan S,Yuan R,Ma YX,et al. BRCA1 genes antagonize phenotype of wild-type BRCA1[J]. Oncogene,2001,20(57): 8215-8235.
[9] Haile DT,Parvin JD.Activation of transcription in vitro by the BRCA1 carboxyl- terminal domain[J].Biol Chem,1999,274: 2113-2117.
[10] Wang H,BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1b are tyrosine phosphor-proteins that associate with E2F,cyclins and cyclin dependent kinase[J].Oncogene,1997,15(2):143-157.
[11] Hsu LC,Doan TP,White RL.Identification of a gamma-tubulin-binding domain in BRCA1[J].Cancer Res,2001,61(21):7713-7718.
[12] Tan W,Zheng L,Lee WH,et al.Functional dissection of transcription factor ZBRK1 reveals zine fingers with dualroles in DNA-binding and BRCA1-dependenttranscriptional repression[J].Biol Chem,2004,279(8): 6576-6587.
[13] Paul TT,Cortez D,Browse B,et al.Direct DNA binding by Brca1[J].Proc Natl AcadSci U S A,2001,98(11):6086-6091.
[14]Hashizume R,Fukuda M,Maeda I,et al.The RING het-erodimer BRCA1-BARD1 is an ubiquitin ligase inactivated by a breast cancer-derived mutation[J]. Biol Chem,2001,276(18): 14537-14540.
[15] Westermark UK,Reyngold M,Olshen AB,et al.BARD1 participates with BRCA1 inhomology-directed repair of chromosome breaks[J].Mol Cell Biol,2003,23(21): 926-936.
[16] Khanna KK,Jackson SP.DNA double stand breaks signal-ing,repair and the cancer connection[J].Nat Genet,2001,27(3): 247-254.
[17] Zhang J,Wilers H,Feng Z,et al.Chk2 phosphorylation of BRCA1 regulates DNA double-strand break repair[J].Mol Cell Biol,2004,24(2): 708-713.
[18] Cantor, Haber, D. A. and Livingston, D. M.et al[J]. BACH1, a novel helicase- like protein, interacts directly with BRCA1 and contributes to its DNA repair function[J]. Cell,2001,1(5): 149-160.
[19] MaLachlan TK,Takimoto R,El-Deiry WS.BRCA1 directs a selective P53-dependenttranscriptional response towards growth arrest and DNA repair targets[J].Mol CellBiol,2002,22(12): 4280-4292.
[20] Arizti P, Fang L, Park I, et al.Tumor suppressor P53 is required to modulate BRCA1 expression[J].Mol Cell Biol,2000,20(20): 7450-7459.
[21] Somasundaram.Arrest of cell cycle by the tumor-suppressor BRCA1 requires the CDK-inhibitor P21WAF1/CiP1[J].Nature,1997,389(6647): 187-190.
[22] Fan W,Jin S,Tong .BRCA1 regulates GADD45 through its interactions with the OCT-1 and CAAT motifs[J].J Biol Chem,2002,277(10): 8061-8067.
[23] Williamson EA,Dadmanesh F,Koeffler HP.BRCA1 transactivates the cyclin-dependent kinase inhibitor P27(Kip1)[J].Oncogene,2002,277(20): 3199-3206.
[24] Zhou C,Liu J.Inhibition of human telomerase reverse transcriptase gene expressionby BRCA1 in human ovarian cancer cells[J].Biochem Biophys Res Commun, 2003 ,303 (1): 30-136.
[25] Fan S,Yuan R,Ma YX,et al.Mutant BRCA1 genes an-tagonize phenotype of wild-type BRCA1[J].Oncogene,2001,20(57): 8215-8235.
[26] Harkin DP,Bean JM.Induction of GADD45 and JNK/SAPK dependent apoptosis following inducible expression of BRCA1[J].Cell,1999,97(5): 575-586.
[27] Yan Y,Haas JP,Kim M,et al.BRCA1-induced apoptosis involves inactivation of ERK1/2 activities[J].Biol Chem,2002,277(36):33422-33430.
[28] Hsu LC,Doan TP,White RL.Identification of a gamma-tubulin-binding domain in BRCA1[J].Cancer Res,2001,61(21): 7713-7718.
[29] Niamh E. Buckley, Alison M. Hosey, Julia J. Gorski, et al BRCA1 Regulates IFN;Signaling through a Mechanism Involving the Type I IFN[J],Mol Cancer Res 2007,5(3): 261–70.
[30] FitzGerald MG, MacDonald DJ,Krainer M, et al. Germ-line brca1 mutations in Jewish and non-Jewish women with early-onset breast cancer[J].New England J med,1996,334(3): 143-149.
[31] Inoue R,Fukutomi T, Ushijima T, et al. Germline mutation of BRCA1 in Japanese breast cancer families [J].Cancer Res,1995,55(16): 3521-3524.
[32] Thompson ME,Jensen RA, Obermiller PS,et al.Decreased expression of BRCA1 accelerates growth and is often present during sporadic breast cancer progression [J].Nat Genet,1995,9 (4): 444-450.
[33]赖春宁,江泽飞,宋三泰,等.186例乳腺癌患者BRCA1基因突变检测[J].中华肿瘤杂志,2001, 23(6): 483-485
[34] Hall JM,Lee MK,Newman B,et al.Linkage of early-onset familial breast cancer tochromosome 17q21[J].Science, 1990, 250(4988): 1684-1689.
[35] Narod SA, Feunteun J,Lynch HT,et al.Familial breast-ovarian cancer locus on chromosome 17q12-q23[J]. Lancet,1991,338(8759): 82-83.
[36] Hall JM, Friedman L, Guenther C.Closing in on a breast cancer gene on chromosome 17q[J]. Am Hum Genet,1992,50(6): 1235-1242.
[37] Easton DF,Bishop DT,Ford P,et al.Genetic linkage analysis in familial breast and ovarian cancer:Results from 214 families[J].Am J Hum Genet,1993,52(4): 678-701
[38] Easton DF,Ford D,Bishop DT,et al.Breast and ovarian cancer incidence in BRCA1mutation carriers[J].Am Hum Genet,1995,56(1): 265-271.
[39] Easton DF,Narod SA,Ford D,et al.The genetic epidemiology of BRCA1[J].Lancet, 1994,344(8924): 761.
[40] Ford D,Easton DF,Bishop DT,et al.Risk of cancer in BRCA1 mutation carrier[J]. Lancet,1994,343(8899): 692-695.
[41] Goldgar DF, Fields P,Lewis CM,et al.A large kindred with 17q-linked breast and ovarian cancer:Genetic phenotypic and genealogical analysis[J].Natl Cancer Inst, 1994,86(3): 200-209.
[42]甄林林,武正炎,范萍等.家族性乳腺癌乳腺癌易感基因-1突变分析[J].中华实验外科杂志,2003,20(2): 170-171.
[43] Yang Hong, Zhou Lei-lei,Liu Jin-ping,et al.Relation ship between the expression of the BRCA1 protein and clinicopathological characteristics of breast cancer[J]. China oncology, 2003,13(1):13-16.
[44]易韦,文安智. BRCA1在散发性乳腺浸润性导管癌癌组织中的表达及意义[J].山东医药, 2008,48(26): 82-83.
[45] Crook T,Crossland S,Crompton M R,Osin P,Gusterson B A.P53 mutations in BRCA1-associated breast cancer[J]. Lancet, 1997,350: 638-639.
[46] Somasundaram K,Zhang H,et al.Arrest of the cell cycle by the tumour suppress-or BRCA1 requires the CDK-in-hibitor P21Waf1/Cip1[J].Nature(Lond),1997,389: 187-190.
[47] Zhang H, Somasundaram K, et al.BRCA1 physically associates with P53 and stim-ulates its transcriptional activity[J]. Oncogene, 1998,16:1713-1721.
[48] Arizti P, Fang L,Park I,et al.Tumor suppressor P53 is required to modulate BRCA1 expression[J]. Mol Cell Biol,2000, 20(20): 7450-7459.
[49] Stoppa-Lyonnet D,Ansquer Y,Dreyfus et al.Familial invasive breast cancer: worse outcome related to BRCA1 mutations[J].Clin Oncol,2000,18(24): 4053-4059.
[50] Kennedy R D,Quinn J E,Mullan P B,et al.The role of BRCA1 in the cellular response to chemotherapy[J].J Natl Cancer Inst,2004,96(22): 1659-1668.
[51] Haffty B G,Yang Q F,Reiss M,et al.Locoregional Relapse and Distant Metastasis in Conservatively Managed Triple Negative Early-Stage Breast Cancer[J]. Clin Oncol,2006,24(36): 5652-5657.
[52] Rodriguez-Pinilla S M,Sarrio D,Honrado E,et al.Prognostic signifficance of basal-like phenotype and fascin expression in node negative invasive breast carcinomas[J].Clin Cancer Res,2006,12(5): 1533-1539.
[53]袁中玉,王树森,高岩,等.305例三阴乳腺癌患者的临床特征及预后因素分析[J].癌症, 2008,27(6): 561-565.
[54] Minn A J,Gupta G P,Siegel P M,et al.Genes that mediate breast cancer metastasisto lung[J].Nature,2005,436(7050): 518-524.
[55] Carey L A, Perou C M, Livasy C A,et al.Race,breast cancer subtypes,and survivalin the Carolina Breast Cancer Study[J]. JAMA,2006,295(21): 2492-2502.
[56] Hoadley KA, Weigman VJ, Fan C, et al.EGFR associated expression profiles vary with breast tumor subtype[J]. BMC Genomics 2007(8): 258–276.
[57] Siziopikou KP, Ariga R, Proussaloglou KE, et al. The challenging estrogen receptor-negative/progesterone receptor-negative/Her-2-negative patient: a promisingcandidate for epidermal growth factor receptor-targeted therapy[J]. Breast 2006(12): 360–362.
[58] Siziopikou KP, Cobleigh M.The basal subtype of breast carcinomas may representthe group of breast tumors that could benefit from EGFR-targeted therapies.Breast2007(16): 104–107.
[59] Miki Y,Swensen J,Shattuck-Eidens D,et al.A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1[J].Science,1994,266(7): 66-71.
[60] Rie I,Takashi F,Toshikazu U,et al.Germline mutation of BRCA1 in Japanese breast cancer families[J].Cancer Res,1995,55: 3521-3524
[61]史玉荣,李臣宾,只向成等.家族性乳腺癌易感基因-1突变的研究[J].中华实验外科杂志,2005,22(10): 1269
[62]胡震,沈镇宙,邵志敏,等.中国家族性和早发性乳腺癌BRCA1基因突变的研究[J].中华肿瘤杂志,2004,26(11): 657-659.
[63] Friedman LS,Szabo CI,Ostermeyer EA,et al.Novel inheri ted mutations and variable expressivity of BRCA1 alleles,including the founder mutation 185delAG in AshkenaziJewish families[J].Am Hum Genet,1995,57: 1284-1297.
[64]王曦,杨名添,方嬿,等.231例乳腺癌患者乳腺癌易感基因BRCA1的突变检测及分析[J].癌症,2001,20(9): 916-920
[65]马怡红,付坚,吴秉铨.53例家族性乳腺癌BRCA1和BRCA2基因部分序列的突变分析[J].北京医科大学学报,2000,32(1): 86
[66] Miki Y,Swensen J,Shattuck-Eidens D,et al.A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1[J].Science,1994,266(7): 66-71.
[67] Shattuck-Eidens D,McClure M,Simard J,et al.A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene[J].JAMA,1995,273(7)∶535-541.
[68] Futreal PA,Liu Q,Shattuck-Eidens D,et al.BRCA1 mutions in primary breast andovarian carcinomas[J].Science,1994,266(7): 120-122.
[69] Takahashi H, Behbakht K,McGovern PE,et al.Mutation analysis of the BRCA1 gene in ovarian cancers[J].Cancer Res,1995,55(14): 2998-3002.
[70] Struewing JP,Brody LC,Erdos MR,et al.Detection of eight BRCA1 mutations in 10breast/ovarian cancer families,including 1 family with male breast cancer[J].Am Hum Genet,1995,57(1): 1-7.
[71] Muto MG,Gramer DW,Tangir J,et al.Frequency of the BRCA1 185 delAG mutation among Jewish women with ovarian cancer and matched population controls[J].Cancer Res,1996,56(6): 1250-1252.
[72] Johnson ,Ostermetyer EA,HaKasson S,et al.Founding BRCA1 mutations in hereditary breast and ovarian cancer in southern Sweden[J].Am J Hum Genet,1996,58(3): 441-450.
[73] Foulkes WD,Stefansson IM,Chappuis PO,et al.Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer[J].Natl Cancer Inst,2003,95(19): 1482-1485.
[74] DaveG,Cosmatos H, Do T,et al.Metaplastic carcinoma of the breast ;A retrospective review[J].Int Radiat oncol Biol Phys,2006,64(3): 771-775.
[75] Kauff ND,Brogi.Epithelial lesions in prophylactic mastectomy specimens from women with BRCA mutations[J].Cancer,2003,97(7): 1601-1608.
[76] Esteva FJ, Sahin AA, Cristofanilli M, et al. Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy[J].Clinic Cancer Res. 2005,(11): 315-319.
[77] Ma XJ, Salunga R, Tuggle JT, et al. Gene expression profiles of human breast cancer progression[J]. Proc Natl Acad Sci USA. 2000, (59): 74-79.