A BRCA1 Splice Site Variant Responsible for Familial Ovarian Cancer in a Han-Chinese Family

• Published in: Current medical science Vol. 42; no. 3; pp. 666 - 672
• Main Authors: Hu, Peng-zhi, Chen, Xiang-yu, Xiong, Wei, Yang, Zhi-jian, Li, Xiao-rong, Deng, Wen-zhi, Gong, Li-na, Deng, Hao, Yuan, La-mei
• Format: Journal Article
• Language: English
• Published: Wuhan Huazhong University of Science and Technology 01.06.2022; Department of Neurology,the Third Xiangya Hospital,Central South University,Changsha 410013,China; Center for Experimental Medicine,the Third Xiangya Hospital,Central South University,Changsha 410013,China; Department of Radiology,the Third Xiangya Hospital,Central South University,Changsha 410013,China%Center for Experimental Medicine,the Third Xiangya Hospital,Central South University,Changsha 410013,China%Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education,Cancer Research Institute and School of Basic Medical Sciences,Central South University,Changsha 410078,China%Department of Gastrointestinal Surgery,the Third Xiangya Hospital,Central South University,Changsha 410013,China%Department of Pathology,the Third Xiangya Hospital,Central South University,Changsha 410013,China%Department of Neurology,the Third Xiangya Hospital,Central South University,Changsha 410013,China%Center for Experimental Medicine,the Third Xiangya Hospital,Central South University,Changsha 410013,China; Disease Genome Research Center,Central South University,Changsha 410013,China
• Subjects: Medicine; Medicine & Public Health; whole-exome sequencing; splice site variant; epithelial ovarian cancer; BRCA1
• ISSN: 2096-5230; 1672-0733; 2523-899X
• DOI: 10.1007/s11596-022-2527-2

Objective Ovarian cancer (OC) is one of the most common and most lethal gynecological malignancies. OC has an age-dependent incidence and occurs more commonly in females older than 50 years old. Most OC patients are diagnosed at an advanced stage and have a poor prognosis. Germline mutations in the BRCA1 DNA repair associated gene ( BRCA1 ) and the BRCA2 DNA repair associated gene ( BRCA2 ) account for 20%–25% of epithelial ovarian cancer (EOC). BRCA1 germline mutations are more common in Chinese EOC patients. Methods This study reported a three-generation Han-Chinese family containing four EOC patients and a rectal adenocarcinoma patient. Whole-exome sequencing was performed on two EOC patients and an unaffected individual. Variant validation was also performed in all available members by Sanger sequencing. Results A heterozygous splice site variant, c.4358-2A>G in the BRCA1 gene, was identified. Bioinformatic analysis showed that the variant may change the splicing machinery. Conclusion The BRCA1 splice site variant, c.4358-2A>G was identified as the likely genetic cause for EOC, and may also be associated with the increased risk of rectal adenocarcinoma in the family. The findings were beneficial for genetic counseling, helpful for cancer prevention in other family members, and may facilitate therapy decision-making in the future to reduce cancer lethality.