Purpose: Breast cancer is the most common type of cancer in women and accounts for 25% of all cancers worldwide. The mechanisms by which it develops include germline (generally inherited) and somatic mutations. There are six mutations with the highest incidence in the Colombian population, called the Colombia profile, which is associated with the BRCA1 and BRCA2 genes. The aim of this study is to identify germline mutations in individuals with breast cancer, such as BRCA and other genes.
Methods: This study describes the frequency and type of variants in hereditary cancer genes associated with breast cancer detected by the next-generation sequencing of a panel of 111 hereditary cancer genes, including BRCA1 and BRCA2.
Results: This analysis allowed the identification of variants associated with breast cancer in 307 patients from a population in southwestern Colombia, of which 19% had pathogenic and probably pathogenic mutations associated with hereditary cancer. According to the variant classification, it was found that the mutation frequency in BRCA1 was 17%, in BRCA2 was 14% and in the ATM gene was 12%; nevertheless, 57% of mutations were attributed to other genes such as MUTYH, FANCM, FANCA and TP53. Four patients were found to have the mutation c.3450delCAAG in the BRCA1 gene, which is included in the Colombia profile.
Conclusion: In summary, in the Colombian population, there is a great diversity of germline mutations in genes other than BRCA1 and BRCA2 that are associated with breast cancer. Studying mutations and variants of uncertain significance in ATM could improve understanding of how mutations in these genes contribute to cancer and whether ATM should be considered as BRCA3.