Mutational analysis of BRCA1 and BRCA2 genes in women with familial breast cancer from different regions of Colombia

Abstract

Purpose The main risk factor for familial breast cancer is the presence of mutations in BRCA1 and BRCA2 genes. The prevalence of mutations in these genes is heterogeneous and varies according to geographical origin of studied families. In Colombia mutations in these genes have been mainly studied on patients from Andean region. Bogotá and Medellin presented its own battery of mutations. This study aims to identify mutations in BRCA1–2 genes in women with familial breast cancer from different regions of Colombia. Methods One hundred four families with a history of breast cancer were sampled in different regions of Colombia, and the BRCA1 gene and exon 11 of the BRCA2 gene were sequenced. To predict the possible effects of sequence alterations found in protein function, different bioinformatics tools were used. Results A total of 33 variants were found; 18 in BRCA1 and 15 in BRCA2, of which 15 are unique variants of Colombia. In silico analysis established that alterations p.Thr790Ala, p.Arg959Lys and p.Glu1345Lys in the BRCA1 gene and variants p.Leu771Phe, p.Asn818Lys, p.Val859Ser*22 and p.Lys1032Ile in the BRCA2 gene are considered likely pathogenic. Both the mutations as the variants of unknown clinical significance, in their great majority, presented a specific region distribution and they were different from those reported in previous studies. Conclusions In this study we report the BRCA1 and BRCA2 spectrum of mutations and their distribution by regions in Colombia. Our results may help to design a diagnostic test including recurrent mutations for screening high risk to breast cancer families in Colombia.

New Perspectives for Resistance to PARP Inhibitors in Triple-Negative Breast Cancer

“…BRCA1/2 genes play a critical role in genome integrity and sustaining chromosomal stability for their primary function of DNA repair, cell cycle control, chromatin remodeling and transcriptional regulation. Thus, mutations in BRCA1/2 result in aberrant expression of proteins and genomic instability, which leads to tumorigenesis (57). Carriers of BRCA1 mutations have a 70-80% chance of developing breast cancer, while those carrying BRCA2 mutations have a 40-84% risk of breast cancer (58).…”

“…Cancers with BRCA1 or BRCA2 mutations exhibit substantial numbers of rearrangement signature 5 deletions (18). The p.Val859Ser*22 mutation of BRCA2, is likely pathogenic and the cause of tumor development, as it generates an early stop codon at position 881 of the BRCA2 protein and truncates proteins with deleterious activity (57). Evidence supports BRCA1/2 mutation as a biomarker for PARPi sensitivity in primary and metastatic breast cancer.…”

Exomes of Ductal Luminal Breast Cancer Patients from Southwest Colombia: Gene Mutational Profile and Related Expression Alterations

“…The disease is the most frequently diagnosed cancer in the vast majority of the countries (154 of 185) and is also the leading cause of cancer death in over 100 countries; the main exceptions are Australia/New Zealand, Northern Europe, Northern America (where it is preceded by lung cancer), and many countries in sub-Saharan Africa (because of elevated cervical cancer rates) [2]. In Colombia, this disease is the second most frequently diagnosed malignancy, representing the leading cause of death in women according to statistics from the National Cancer Institute (INC) from Colombia [3] that estimated around 7600 new breast cancer cases diagnosed annually in the period 2007-2011, with 2226 annual breast cancer deaths [4].…”

Soluble IL-2R as a predictor of familial breast cancer

“…BRCA1/2 genes account for approximately 25% of all cases of FBC. Families with mutations in these genes usually have several members affected; carriers of mutations in BRCA1 have a 70-80% chance of developing the disease [8,9]. BRCA1 is also involved in another type of DNA repair, termed mismatch repair.…”