Peng-Zhi Hu1,2, Xiang-Yu Chen1, Wei Xiong3, Zhi-Jian Yang1, Xiao-Rong Li4, Wen-Zhi Deng5, Li-Na Gong6, Hao Deng1,6,7, La-Mei Yuan8. 1. Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, 410013, China. 2. Department of Radiology, the Third Xiangya Hospital, Central South University, Changsha, 410013, China. 3. 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. 4. Department of Gastrointestinal Surgery, the Third Xiangya Hospital, Central South University, Changsha, 410013, China. 5. Department of Pathology, the Third Xiangya Hospital, Central South University, Changsha, 410013, China. 6. Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, 410013, China. 7. Disease Genome Research Center, Central South University, Changsha, 410013, China. 8. Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, 410013, China. yuanlamei229@163.com.
Abstract
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.
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.
Authors: Christian F Singer; Yen Y Tan; Daniela Muhr; Christine Rappaport; Daphne Gschwantler-Kaulich; Christoph Grimm; Stephan Polterauer; Georg Pfeiler; Andreas Berger; Muy-Kheng M Tea Journal: Cancer Med Date: 2019-03-01 Impact factor: 4.452