Panel sequencing of 264 candidate susceptibility genes and segregation analysis in a cohort of non-BRCA1, non-BRCA2 breast cancer families.
Panel sequencing of 264 candidate susceptibility genes and segregation analysis in a cohort of non-BRCA1, non-BRCA2 breast cancer families.
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DOI：
10.1007/s10549-017-4469-0
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发表时间：
2017-12
影响因子：
3.8
通讯作者：
Chenevix-Trench G
中科院分区：
文献类型：
--
作者：
Li J;Li H;Makunin I;kConFab Investigators;Thompson BA;Tao K;Young EL;Lopez J;Camp NJ;Tavtigian SV;John EM;Andrulis IL;Khanna KK;Goldgar D;Chenevix-Trench G
本研究的主要目的是在非BRCA1/2(BRCAx)乳腺癌家系中筛选表观遗传修饰基因和已知乳腺癌致癌基因的胚系突变，以确定新的中高外显性易感基因。我们从656例非BRCA1/2家系中筛选出264个候选易感基因。然后在所有可用的家族成员中对潜在致病候选突变进行基因分型，以评估该变异与家族内疾病的共分离，以便估计与这些突变相关的乳腺癌风险。对于11个候选易感基因，我们额外筛选了800例非BRCA1/2乳腺癌病例和787名对照。只有CHD8和USH2A两个基因显示乳腺癌风险增加(RR分别为2.40(95%可信区间1.0~7.32)和2.48(95%可信区间1.11~6.67))。我们没有发现令人信服的证据表明表观遗传修饰基因和已知的乳腺癌驱动基因携带胚系突变，从而增加乳腺癌风险。USH2A不再被认为是乳腺癌的驱动基因，考虑到它与亚瑟综合征的关联，它似乎是一个不可信的候选基因。然而，最近报道了CHD8的体细胞突变，使其成为更有希望的候选基因，但需要在非常大的家庭队列中进行进一步的CHD8分析或病例对照研究，以确定它是否是中等风险的乳腺癌易感基因。
The main aim of this study was to screen epigenetic modifier genes and known breast cancer driver genes for germline mutations in non-BRCA1/2 (BRCAx) breast cancer families in order to identify novel susceptibility genes of moderate-high penetrance. We screened 264 candidate susceptibility genes in 656 index cases from non-BRCA1/2 families. Potentially pathogenic candidate mutations were then genotyped in all available family members for the assessment of co-segregation of the variant with disease in the family in order to estimate the breast cancer risks associated with these mutations. For 11 of the candidate susceptibility genes, we screened an additional 800 non-BRCA1/2 breast cancer cases and 787 controls. Only two genes, CHD8 and USH2A showed any evidence of an increased risk of breast cancer (RR = 2.40 (95% CI 1.0–7.32) and 2.48 (95% CI 1.11–6.67), respectively). We found no convincing evidence that epigenetic modifier and known breast cancer driver genes carry germline mutations that increase breast cancer risk. USH2A is no longer regarded as a breast cancer driver gene and seems an implausible candidate given its association with Usher syndrome. However, somatic mutations in CHD8 have been recently reported, making it an even more promising candidate, but further analysis of CHD8 in very large cohorts of families or case-control studies would be required to determine if it is a moderate-risk breast cancer susceptibility gene.
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DOI：
10.1097/pas.0b013e3182380802
发表时间：
2012-01
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Carter JM;O'Hara C;Dundas G;Gilchrist D;Collins MS;Eaton K;Judkins AR;Biegel JA;Folpe AL
通讯作者：
Folpe AL
影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
影响因子：
12.3
作者：
Daxinger L;Harten SK;Oey H;Epp T;Isbel L;Huang E;Whitelaw N;Apedaile A;Sorolla A;Yong J;Bharti V;Sutton J;Ashe A;Pang Z;Wallace N;Gerhardt DJ;Blewitt ME;Jeddeloh JA;Whitelaw E
通讯作者：
Whitelaw E
DOI：
10.1534/g3.112.004036
发表时间：
2012-11
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Daxinger L;Oey H;Apedaile A;Sutton J;Ashe A;Whitelaw E
通讯作者：
Whitelaw E
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A