BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic-related mutations in BRCA1 associated with an increased risk of ovarian cancer.
BRCA1/2 are cancer predisposition genes involved in hereditary breast and ovarian cancer (HBOC). Mutation carriers display an increased sensitivity to inhibitors of poly(ADP-ribose) polymerase (PARP). Despite a number of small-size hospital-based studies being previously reported, there is not yet, to our knowledge, precise data of BRCA1/2 mutations among Chinese ovarian cancer patients. We performed a multicenter cohort study including 916 unselected consecutive epithelial ovarian cancer (EOC) patients from eastern China to screen for BRCA1/2 mutations using the next-generation sequencing approach. A total of 153 EOC patients were found to carry pathogenic germline mutations in BRCA1/2, accounting for an overall mutation incidence of 16.7% with the predominance in BRCA1 (13.1%) compared with BRCA2 (3.9%). We identified 53 novel pathogenic mutations, among which the c.283_286delCTTG and the c.4573C > T of BRCA1 were both found in two unrelated patients. More importantly, the most common mutation found in this study, c.5470_5477del8 was most likely to be Chinese population-related without an apparent founder origin. This hot-spot mutation was presumably associated with an increased risk of ovarian cancer. Taken together, germline BRCA1/2 mutations were common in Chinese EOC patients with distinct mutational spectrum compared to Western populations. Our study contributes to the current understanding of BRCA1/2 mutation prevalence worldwide. We recommend BRCA1/2 genetic testing to all Chinese women diagnosed with EOC to identify HBOC families, to provide genetic counseling and clinical management for at-risk relatives. Mutation carriers may also benefit from PARP-targeted therapies.
Ovarian Cancer Program, Division of Gynecologic Oncology, Department of Gynecology & Obstetrics, Zhongshan hospital, Fudan University, Shanghai, 200032, China.
Tingyan
T
Shi
Ovarian Cancer Program, Division of Gynecologic Oncology, Department of Gynecology & Obstetrics, Zhongshan hospital, Fudan University, Shanghai, 200032, China.
Pan
P
Wang
Shanghai Topgen Bio-Pharm Co, Ltd, Shanghai, China.
Caixia
C
Xie
Ovarian Cancer Program, Division of Gynecologic Oncology, Department of Gynecology & Obstetrics, Zhongshan hospital, Fudan University, Shanghai, 200032, China.
Sheng
S
Yin
Ovarian Cancer Program, Division of Gynecologic Oncology, Department of Gynecology & Obstetrics, Zhongshan hospital, Fudan University, Shanghai, 200032, China.
Di
D
Shi
Shanghai Topgen Bio-Pharm Co, Ltd, Shanghai, China.
Congchong
C
Wei
Ovarian Cancer Program, Division of Gynecologic Oncology, Department of Gynecology & Obstetrics, Zhongshan hospital, Fudan University, Shanghai, 200032, China.
Wenbin
W
Tang
Ovarian Cancer Program, Division of Gynecologic Oncology, Department of Gynecology & Obstetrics, Zhongshan hospital, Fudan University, Shanghai, 200032, China.
Rong
R
Jiang
Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Xi
X
Cheng
Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.|Duke Cancer Institute, Duke University Medical Center, Durham, NC.
Qingyi
0000-0002-3845-9445
Q
Wei
Plateforme de génomique des cancers, Centre Léon Bérard, Laboratoire de la génétique constitutionnelle HCL-CLB, Lyon, France.
Qing
Q
Wang
Ovarian Cancer Program, Division of Gynecologic Oncology, Department of Gynecology & Obstetrics, Zhongshan hospital, Fudan University, Shanghai, 200032, China.|Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Rongyu
0000-0002-1334-2398
R
Zang
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D002681:China / Q000453:epidemiology; D005006:Ethnicity / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000627:therapeutic use
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D011065:Poly(ADP-ribose) Polymerases
BRCA1 gene; BRCA2 gene; mutation; ovarian cancer