Abstract
This study aimed to characterize women at-risk for hereditary BC regarding their clinical and molecular characteristics (mutation and methylation in the BRCA1 gene) and correlate the gene expression levels with histopathological, clinical and family history information. BRCA1 real time qPCR was performed to evaluate methylation status and gene expression. The study included 88 women grouped according to the BRCA1 mutational status: 23 BRCA1 mutated, 22 with a Variant of Unknown Significance (VUS) in BRCA1 and 43 BRCA1 WT. Most BRCA1 mutated tumors were triple negative (69.6%) and had histologic grade III (61.0%). Patients with VUS/WT BRCA1 were predominantly of luminal B subtype with histological grades I and II. Regarding the methylation profile, BRCA1 hypermethylation was observed in only two patients (both WT) and none had association with pathogenic BRCA1 mutation. In one patient methylation was present in both, tumor and normal tissues. Hypermethylated tumors had ductal histology, negativity for ER and occurred in < 50 years patients. Gene expression profile showed in all groups lower BRCA1 mRNA levels in tumor tissue compared to the adjacent breast tissue, thereby indicating the loss/decrease of gene function. No association was found between the levels of BRCA1 gene expression and family history of cancer. In summary, our findings suggested that methylation at the BRCA1 gene is not the “second” event in the development of BC in patients with germline mutations in BRCA1 and, although rare, BRCA1 epimutations can constitute an explanation for a fraction of HBOC families.
Highlights
Breast cancer (BC) is the most common malignancy in women, accounting for 22% of new cases of cancer each year [1]
Our findings suggested that methylation at the BRCA1 gene is not the "second" event in the development of BC in patients with germline mutations in BRCA1 and, rare, BRCA1 epimutations can constitute an explanation for a fraction of Hereditary Breast and Ovarian Cancer Predisposition Syndrome (HBOC) families
Estrogen (ER) and progesterone (PR) were predominantly negative in the BRCA1-pathogenic group, unlike that observed in the BRCA1-Variant of Unknown Significance (VUS) and BRCA1-WT groups (p = 0.008 and p = 0.003, respectively; Table 2)
Summary
Breast cancer (BC) is the most common malignancy in women, accounting for 22% of new cases of cancer each year [1]. Germline mutations in the tumor suppressor genes, BRCA1 and BRCA2 account for approximately 20% of cases of hereditary breast cancer cases [3]. Germline mutation in BRCA1 gene carriers have a cumulative risk of developing breast cancer ranging from 44% to 68% by 70 years of age [4]. Mutations in BRCA1 and BRCA2 genes are associated with the Hereditary Breast and Ovarian Cancer Predisposition Syndrome (HBOC). HBOC families, like other families with hereditary cancer predisposition syndromes, are characterized by early age on diagnosis, multiple primary tumors, bilateral tumors or multiple rare tumors and two or more generations affected by cancer [5, 6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
