Clinical Characteristics of Ovarian Cancer Classified by BRCA1, BRCA2, and RAD51C Status

被引：118

作者：

Cunningham, J. M. ^{[1
]}

Cicek, M. S. ^{[2
]}

Larson, N. B. ^{[3
]}

Davila, J. ^{[3
]}

Wang, C. ^{[3
]}

Larson, M. C. ^{[3
]}

Song, H. ^{[4
]}

Dicks, E. M. ^{[4
]}

Harrington, P. ^{[4
]}

Wick, M. ^{[5
]}

Winterhoff, B. J. ^{[5
]}

Hamidi, H. ^{[6
]}

Konecny, G. E. ^{[6
]}

Chien, J. ^{[7
]}

Bibikova, M. ^{[8
]}

Fan, J. -B. ^{[8
]}

Kalli, K. R. ^{[9
]}

Lindor, N. M. ^{[10
]}

Fridley, B. L. ^{[11
]}

Pharoah, P. P. D. ^{[4
,12
]}

Goode, E. L. ^{[2
]}

机构：

[1] Mayo Clin, Dept Pathol & Lab Med, Div Expt Pathol, Rochester, MN USA

[2] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN 55905 USA

[3] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA

[4] Univ Cambridge, Dept Oncol, Cambridge, England

[5] Mayo Clin, Dept Obstet & Gynecol, Rochester, MN USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA

[7] Univ Kansas, Med Ctr, Dept Translat Genom, Kansas City, KS 66103 USA

[8] Illumina Corp, San Diego, CA USA

[9] Mayo Clin, Dept Med Oncol, Rochester, MN USA

[10] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[11] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66103 USA

[12] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England

来源：

SCIENTIFIC REPORTS | 2014年 / 4卷

基金：

美国国家卫生研究院;

关键词：

SUSCEPTIBILITY GENE; GERMLINE MUTATIONS; CONFER SUSCEPTIBILITY; BREAST; IDENTIFICATION; METHYLATION; HEREDITARY; CARCINOMA; SURVIVAL; BRCANESS;

D O I：

10.1038/srep04026

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n=5899), somatic mutations (n=5279) and epigenetic alterations (n=5 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.

引用

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