title: Screening of BRCA1/2 Mutations Using Direct Sequencing in Indonesian Familial Breast Cancer Cases.
abstract: Breast cancer has emerged as the most prevalent cancer among women worldwide, including in Indonesia. The contribution of genes associated with high-risk breast-ovarian cancers, BRCA1 and BRCA2, in the Indonesian population is relatively unknown. We have characterized family history of patients with moderate- to high-risk of breast cancer predisposition in 26 unrelated cases from Indonesia for BRCA1/2 mutation analyses using direct sequencing. Known deleterious mutations were not found in either BRCA1 or BRCA2 genes. Seven variants in BRCA2 were documented in 10 of 26 patients (38%). All variants were categorized as unclassified (VUSs). Two synonymous variants, c.3623A>G and c.4035T>C, were found in 5 patients. One variant, c4600T>C, was found in a 38 year old woman with a family history of breast cancer. We have found 4 novel variants in BRCA2 gene including c.6718C>G, c.3281A>G, c.10176C>G, and c4490T>C in 4 unrelated patients, all of them having a positive family history of breast cancer. In accordance to other studies in Asian population, our study showed more frequent variants in BRCA2 compared to BRCA1. Further studies involving larger numbers of hereditary breast cancer patients are required to reveal contribution of BRCA1/2 mutations and/or other predisposing genes among familial breast cancer patients in Indonesia.
authors.affiliation: Department of Surgery, Faculty of Medicine Universitas Gadjah Mada, Yogyakarta, Indonesia E-mail : sl.anwar@ugm.ac.id.
authors.forename: Sumadi Lukman
authors.initials: SL
authors.lastname: Anwar
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Haryono
authors.forename: Teguh
authors.initials: T
authors.lastname: Aryandono
authors.forename: I Gusti Bagus
authors.initials: IG
authors.lastname: Datasena
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis / Q000235:genetics; D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000235:genetics; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis / Q000235:genetics; D018276:Carcinoma, Medullary / Q000175:diagnosis / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007214:Indonesia; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor