PT  - JOURNAL ARTICLE
AU  - Di Shao
AU  - Shaomin Cheng
AU  - Fengming Guo
AU  - Yuying Yuan
AU  - Kunling Hu
AU  - Zhe Wang
AU  - Xuan Meng
AU  - Xin Jin
AU  - Yun Xiong
AU  - Xianghua Chai
AU  - Hong Li
AU  - Yu Zhang
AU  - Hongyun Zhang
AU  - Jihong Liu
AU  - Mingzhi Ye
TI  - Frequency of mutations in 21 hereditary breast and ovarian cancer susceptibility genes among high-risk Chinese individuals
AID  - 10.1101/514539
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 514539
4099  - http://biorxiv.org/content/early/2019/04/29/514539.short
4100  - http://biorxiv.org/content/early/2019/04/29/514539.full
AB  - To determine the prevalence and clinical prediction factors associated with deleterious mutations among 882 high-risk Chinese individuals who underwent multigene panel testing for hereditary breast and ovarian cancer (HBOC) risk assessment. Subjects were selected from individuals referred for genetic testing using a 21-gene panel (Oseq-BRCA) between January 2015 and March 2018. The distribution and prevalence of deleterious mutations were analyzed for the full cohort as well as subtypes. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) individuals. Of these, 26 mutations are not reported in public databases and literatures. In the ovarian cancer only subgroup, 115 deleterious mutations were identified in 429 patients (48.6%). Patients with ovarian cancer with mutations were enriched for a family history of breast or ovarian cancers (p < 0.05). In the breast cancer only subgroup, 31 deleterious mutations were identified in 261 patients. Most mutations occurred in BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%). An additional 12 deleterious mutations (38.7%) were found in 7 other susceptibility genes. An increased frequency of mutation rate (57.9%) was observed in the subgroup of subjects with histories of both breast and ovarian cancer. Taken together, 19.50% of individuals carried a deleterious mutation in HBOC susceptibility genes in our cohort. Subgroup of subjects with histories of both breast and ovarian cancer had the highest prevalence of mutations. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of multigene panel in performing risk assessment.HBOChereditary breast and ovarian cancerPARPpoly-ADP-ribose polymerasePCRpolymerase chain reactionDGGEdenaturing gradient gel electrophoresisNCCNNational Comprehensive Cancer NetworkTRFstest requisition formsInDelsinsertions and deletionsGATKGenome Analysis ToolkitCNVscopy number variantsHGVSHuman Genome Variation SocietyACMGAmerican College of Medical GeneticsVUSvariant of uncertain significanceHRhomologous recombinationFAFanconi anaemia