Identification of twenty-nine novel germline unclassified variants of BRCA1 and BRCA2 genes in 1400 Italian individuals

摘要

Abstract Objectives Breast and/or ovarian cancers are complex multifactorial diseases caused by interaction of both genetic and non-genetic factors and characterized by predisposition to inheritance. BRCA1 and BRCA2 genes are the most clinically involved with these kinds of cancer and the spectrum of variants affecting these genes is very wide. In fact, point variants, large or small insertions/deletions, genomic rearrangements can be found in these patients, although a large number of variants with uncertain biological and clinical significance continues to be identified. Next-generation sequencing (NGS) technology is actually the most powerful tool for the discovering of causative mutations and novel disease genes, moreover it allows to make a rapid diagnosis of genetic variants giving fast, inexpensive and detailed genetic information. Material and methods In this study, we report the screening of BRCA1 and BRCA2 genes on 1400 consecutive Caucasian patients with breast and/or ovarian cancer history or family risk, attending the oncogenetic ambulatory at the Foundation Policlinico Agostino Gemelli in Rome. Results We describe twenty-nine novel BRCA1 and BRCA2 variants detected in Italian individuals suffering from hereditary breast and ovarian cancer syndrome (HBOC). Conclusion Data regarding novel variants can provide useful information not only at epidemiological but also at clinical level, allowing for the better managing of breast and ovarian cancer patients and their family members. Highlights ? BRCA1 and BRCA2 genes screening in 1400 individuals suffering from HBOC is reported. ? Twenty-nine novel variants were identified in twenty-nine Italian patients. ? The screening programs would play an important role in HBOC detection and prevention.