OBJECTIVE: To explore the genetic basis for a male with breast cancer and a sister who had deceased of the disease. METHODS: Medical and family history of the proband was collected. Next-generation sequencing was carried out to detect potential variant associated with breast cancer, and Sanger sequencing was used to verify the result. RESULTS: The proband was found to harbor a novel heterozygous c.6018dupT variant of the BRCA2 gene which may cause premature termination of mRNA translation, resulting in a truncated protein. Combined with the family history, the variant was deduced to be a germline mutation. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.6018dupT variant of BRCA2 gene was predicted to be pathogenic (PVS1+PM1/2+PP4). CONCLUSION The germline variant of the BRCA2 gene probably underlay the breast cancer in this pedigree.
BRCA2 Protein/genetics* ; Breast Neoplasms, Male/genetics* ; Genes, BRCA2 ; Genomics ; Germ Cells ; Germ-Line Mutation ; Humans ; Male

Breast Neoplasms ; genetics ; Disease Susceptibility ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Mutation ; Ovarian Neoplasms ; genetics

Animals ; Genes, BRCA2 ; Genes, erbB-1 ; Genes, erbB-2 ; Genes, p16 ; Genes, p53 ; Genes, ras ; Genetic Predisposition to Disease ; genetics ; Humans ; Pancreatic Neoplasms ; classification ; genetics ; pathology

Approximately 7% of all breast cancer cases are associated with hereditary predisposition and BRCA1 and BRCA2 gene, which accounts for half of the hereditary breast cancer (HBC). Although majority of breast cancer occur sporadically, identification of HBC is important in that active adoption of preventive strategies such as surveillance, chemoprevention, and riskreducing surgery will result in the gain of life-expectancy. According to the recent studies, the prevalence and penetrance of BRCA mutation in Korean breast cancer patients are comparable to that of western countries. Genetic testing should be done in the setting of genetic counseling, which provides the patients with comprehensive information about the test procedure, the interpretation of the test result, and possible options when the test results were positive for mutation. The management of HBC is not different from that of sporadic cancer and many clinical trials investigating the chemoprevention and targeted therapy of HBC are underway. The Korean Hereditary Breast Cancer (KOHBRA) study is a nationwide multicenter study to reveal the prevalence of BRCA mutation in Korean breast cancer patients. After the completion of the KOHBRA study, we expect important basic data which will be the backbone of clinical practice guideline for Korean HBC patients.
Adoption ; Breast ; Breast Neoplasms ; Chemoprevention ; Genes, BRCA2 ; Genetic Counseling ; Genetic Testing ; Humans ; Penetrance ; Prevalence

We recently experienced a case of endometrial cancer 5 years after the diagnosis of breast cancer in a patient with a mutation in the BRCA2 gene. A 55-year-old Korean woman who had a past history of breast cancer in her 50s underwent an operation for endometrial cancer. Final pathology confirmed stage Ia, and no adjuvant treatment was performed. After surgery, considering her history of sequential cancer occurrence, genetic counseling was offered. The result showed the BRCA2 variation of unknown significance mutation. This is the first case report of sequential cancers (endometrial and breast) in a patient with a BRCA2 mutation among a Korean population.
Breast Neoplasms* ; Diagnosis ; Endometrial Neoplasms* ; Female ; Genes, BRCA2 ; Genetic Counseling ; Humans ; Middle Aged ; Pathology

Fanconi anemia (FA) is a rare genetic disease with both autosomal and X-linked inheritance, characterized by genomic instability. The cells from individuals with FA are highly sensitive to DNA-crosslinking drugs, such as mitomycin C (MMC), diepoxybutane (DEB) and so on. Now at least 13 genes (FA-A, B, C, D1, D2, E, F, G, I, J, L, M, N) have been identified, whose products participate in a DNA damage-response network involving breast cancer susceptibility gene products, BRCA1 and BRCA2. The impaired DNA repair due to mutations in FA genes is thought to be one of the main pathogenesis of FA, also closely related to the development of some cancers. In this review, the advances of study about FA-BRCA network are summarized.
DNA Damage ; DNA Repair ; Fanconi Anemia ; genetics ; pathology ; Genes, BRCA2 ; Humans

No abstract available.
Genes, Tumor Suppressor ; BRCA2 Protein ; BRCA1 Protein ; Ovarian Neoplasms ; Breast Neoplasms

Most studies related to BRCA mutations have been performed in Western populations, and only a few small studies have been conducted in Korean populations. In 2007, the Korean Hereditary Breast Cancer (KOHBRA) Study was established to obtain evidence for the accurate risk assessment and management of hereditary breast and ovarian cancer (HBOC) in Korea. Between May 2007 and May 2010, the first phase of the KOHBRA Study was performed to estimate the prevalence of BRCA1/2 mutations among patients and their families at risk for HBOC. Between June 2010 and May 2013, the second phase of the KOHBRA Study was performed to identify the clinical characteristics and prognostic indicators of BRCA-related breast cancer and environmental and genetic modifiers of BRCA mutations and to develop a Korean BRCA risk calculator and nationwide genetic counseling network for HBOC. Herein, we review the results of the KOHBRA Study and describe the future perspectives of the study.
Breast ; Breast Neoplasms ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic Counseling ; Humans ; Korea ; Neoplastic Syndromes, Hereditary ; Ovarian Neoplasms ; Prevalence ; Risk Assessment

PURPOSE: Unclassified variants (UVs) of BRCA1 and BRCA2 genes are not defined as pathogenic for breast cancer, and their clinical significance currently remains undefined. Therefore, this study was conducted to identify potentially pathogenic UVs by comparing their prevalence between breast cancer patients and controls. MATERIALS AND METHODS: A total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center of Korea. Genetic variants of BRCA genes that were categorized as unclassified according to the Breast Cancer Information Core database were selected based on allelic frequency, after which candidate variants were genotyped in 421 healthy controls. We also examined family members of the study participants. Finally, the effects of amino acid substitutions on protein structure and function were predicted in silico. RESULTS: Genetic tests revealed 33 UVs in BRCA1 and 47 in BRCA2. Among 15 candidates genotyped in healthy controls, c.5339T>C in BRCA1 and c.6029T>G, c.7522G>A in BRCA2 were not detected. Moreover, the c.5339T>C variant in the BRCA1 gene was detected in four patients with a family history of breast cancer. This nonsynonymous variant (Leu1780Pro) in the BRCA1 C-terminal domain was predicted to have an effect on BRCA1 protein structure/function. CONCLUSION: This study showed that comparison of genotype frequency between cases and controls could help identify UVs of BRCA genes that are potentially pathogenic. Moreover, ourfindings suggest that c.5339T>C in BRCA1 might be a pathogenic variant for patients and their families.
Amino Acid Substitution ; BRCA1 Protein ; Breast Neoplasms* ; Breast* ; Computer Simulation ; Genes, BRCA1 ; Genes, BRCA2* ; Genetic Testing ; Genotype ; Humans ; Korea ; Prevalence

OBJECTIVE: BRCA mutational status is important in the management of ovarian cancer, but there is a lack of evidence supporting genetic testing in Asian populations. This study was performed to investigate the prevalence and prognostic outcomes of BRCA1/2 mutation and variant of unknown significance (VUS) in Korean patients diagnosed with epithelial ovarian cancer (EOC). METHODS: Among patients newly diagnosed with EOC between January 2007 and January 2017, those tested for germline BRCA1/2 mutation were studied, regardless of family history. Overall survival (OS) and progression-free survival (PFS) were compared between the patients with and without BRCA1/2 mutation and VUS. RESULTS: A total of 313 patients underwent BRCA testing: 88 patients had a BRCA1/2 mutation and 48 patients had a BRCA1/2 VUS (28.1% and 15.3%, respectively). There were no significant associations between BRCA1/2 mutation, BRCA1/2 wild-type, or BRCA1/2 VUS with age at diagnosis, histologic distribution, or residual disease status after primary cytoreductive surgery. BRCA1 mutation, including BRCA1 VUS, showed no difference in PFS or OS compared to BRCA1 wild-type. In contrast, BRCA2 mutation showed longer PFS than that of BRCA2 wild-type (P=0.04) or BRCA2 VUS (P=0.02). BRCA2 mutation, including BRCA2 VUS, did not show any difference in OS compared to BRCA2 wild-type. CONCLUSION: BRCA mutation and BRCA VUS had similar clinical characteristics and survival outcomes, except that BRCA2 mutation showed better PFS. The results of this study will help to understand the prognostic significance of BRCA mutation and VUS in Korean patients.
Asian Continental Ancestry Group ; Diagnosis ; Disease-Free Survival ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic Testing ; Humans ; Korea ; Ovarian Neoplasms ; Prevalence