The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels

Abstract

An important role of genetic factors in the development of breast cancer (BC) or ovarian cancer (OC) in Taiwanese (ethnic Chinese) patients has been suggested. However, other than germline BRCA1 or BRCA2 mutations, which are related to hereditary breast-ovarian cancer (HBOC), cancer-predisposition genes have not been well studied in this population. The aim of the present study was to more accurately summarize the prevalence of genetic mutations in HBOC patients using various gene panels ranging in size from BRCA1/2 alone to multi-gene panels. Among 272 HBOC patients analyzed, the prevalence of BRCA1, BRCA2 and non-BRCA1/2 pathogenic mutations was 7.7% (21/272), 6.8% (16/236) and 8.2% (13/159), respectively. The total mutation rate was 18.4% (50/272). Although no founder mutations were identified in this study, two recurrent mutations, BRCA1 (c.3607C>T) and BRCA2 (c.5164_5165 delAG), were found. The main pathogenic/likely pathogenic mutations in non-BRCA1/2 genes included ATM, BRIP1, FANCI, MSH2, MUYTH, RAD50, RAD51C and TP53. The prevalence rate of gene mutations in HBOC patients did not differ with respect to whether BC or OC was the first diagnosis or they presented a family history of the disease or their age at diagnosis. HBOC patients with both BC and OC exhibited a higher prevalence rate of mutations (50.0%) than patients with OC (25.0%) or BC (8.6%) alone. In conclusion, evaluation of hereditary cancer risk in Taiwan HBOC patients, particularly individuals with double cancer, is strongly encouraged. Panel testing can yield additional genomic information, and widespread and well-designed panel testing will help in assessing more accurate mutational prevalence of risk genes.

Large-scale meta-analysis of mutations identified in panels of breast/ovarian cancer-related genes — Providing evidence of cancer predisposition genes

“…Differences in the selection of particular genes emphasize the lack of sufficient information about the association of many genes with a particular type of cancer. As MGP sequencing is becoming more popular, the results of few new studies [8][9][10][11][12][13][14], including one cumulative, large-scale analysis [5], were published during the preparation of the manuscript. The results of these studies are not included in the meta-analysis, but we refer to them in the discussion.…”

Prevalence and Spectrum of BRCA Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric Study

“…We focused our study on variant detection rates and genetic characteristics associated with specific selection criteria for BRCA1/2 testing in high-risk families and patients affected by breast cancer, whereas other authors evaluated clinical implications and strategy of surveillance of women at high risk. Thirteen percent of the individuals evaluated were carriers of a pathogenic variant, according to the range shown in other countries [ 27 , 28 , 29 , 30 ], excluding Ashkenazi Jewish ancestry in which founder variants were prevalent [ 31 ]. The incidence of BRCA1 and BRCA2 variants was 7.7% and 6.3%, respectively.…”

Comparing Paclitaxel–Carboplatin with Paclitaxel–Cisplatin as the Front-Line Chemotherapy for Patients with FIGO IIIC Serous-Type Tubo-Ovarian Cancer

“…Serous-type is the most common subtype among EOCs in general; however, endometriosis-associated EOCs, such as clear cell type or endometrioid type are relatively common in certain populations, including Taiwan and Japan [7][8][9][10][11]. Clinically, the serous-type EOC and primary peritoneal serous carcinoma (PPSC) and primary Fallopian tube cancer (PFTC) are often considered the same group disease, based on the similar clinical behavior and possibly sharing the similar pathogenesis [12][13][14][15][16][17][18]. In 1996, McGuire and colleagues conducted a clinical trial to set up the standard therapy for patients with ETOC, including primary debulking surgery (PDS), also called primary cytoreductive surgery (PCS) plus adjuvant triweekly paclitaxel and cisplatin therapy [19].…”