Prevalence of pathogenic non-BRCA1/2 gene variants in patients with suspected hereditary breast and ovarian cancer at a referral hospital in northeastern Brazil.

Abstract

e13602 Background: Breast cancer (BC) is associated with several hereditary syndromes (HS). Patients with clinical criteria for hereditary breast and ovarian cancer (HBOC) should be evaluated for the presence of pathogenic BRCA1/2 variants, although the absence of BRCA1/2 variants does not rule out HS. The purpose of this study was to evaluate the prevalence of pathogenic non- BRCA1/2 variants in patients with suspected HBOC. Methods: Suspected HBOC (NCCN criteria) patients (n = 267) from a Northeastern Brazilian referral cancer hospital were submitted to NGS 31-gene painel. Individuals testing negative for BRCA1/2 mutation (n = 210) remained in the present presentation. Data were analized by the chi-squared test and Fisher’s test ( p< 0.05; SPSS 20.0). Results: Pathogenic/likely pathogenic (P/LP) non- BRCA1/2 variants were detected in 13.3% (n = 28/210) of the patients, all of whom had BC. The most prevalent variant was PALB2 (31%), followed by ATM and MUTYH (14.2%), and TP53 and PMS2 (10.7%). Among these patients 10.7% (n = 3/28) had triple negative tumors. Other gene variants ( BARD1, CHEK2, MLH1, MSH2, PMS1 and XRCC2) were observed at lower frequencies (3.5% each). DNA mismatch repair (MMR)/Lynch syndrome (LS) mutated genes were identified in 4/24 patients with BC. Rare microdeletions were identified in PALB2 (chr16:23652431-23652678 [exons 1-10] and TP53 (chr17:7.573.927-7.579.891 [exons 2-10]) , to our knowledge for the first time in the medical literature (ClinVar). In addition, one patient displayed a double pathogenic variant in ATM (c.67C > T: p.[Arg23*]) and PALB2 (chr16:23652431-23652678 [exons 1-10]). Patients with and without P/LP did not differ with regard to clinical-pathological parameters or therapeutic profile. Conclusions: Patients with suspected HBOC should be evaluated for non- BRCA1/2 variants, including MMR. We also suggest considering BC among the malignancies associated with LS.