Detection of a large rearrangement in PALB2 in Spanish breast cancer families with male breast cancer

et al.It has been demonstrated that monoallelic PALB2 (Partner and Localizer of BRCA2) gene mutations predispose to familial breast cancer. Some of the families reported with germline PALB2 mutations presented male breast cancer as a characteristic clinical feature. Therefore, we wanted to investigate the contribution of germline PALB2 mutations in a set of 131 Spanish BRCA1/BRCA2-negative breast/ovarian cancer families with at least one male breast cancer case. The analysis included direct sequencing of all coding exons and intron/exon boundaries as well as a Multiplex Ligation-dependent Probe Amplification-based analysis of genomic rearrangements. For the first time we have identified a genomic rearrangement of PALB2 gene involving a large deletion from exon 7 to 11 in a breast cancer family. We have also identified several PALB2 variants, but no other obvious deleterious PALB2 mutation has been found. Thus, our study does not support an enrichment of PALB2 germline mutations in the subset of breast cancer families with male breast cancer cases. The identification of intronic and exonic variants indicates the necessity of assessing the implications of variants that do not lead to PALB2 truncation in the pathoghenicity of the PALB2 gene.This study was supported by grants from the Xunta de Galicia (10PXIB 9101297PR) and FMM Foundation given to AV. TC, M de H, and PPS were supported by PS09/00859, RD06/0020/0021 from RTICC, Instituto de Salud Carlos III. JB and AO were supports by the AECC, and RD06/0020/1060 from RTICC ICO: Contract grant sponsor: Asociación Española Contra el Cáncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/ 31488, and 2009SGR290. E.V. grants, CSI004A10-2 (Consejería de Educación, Junta de Castilla y León) and BIO39/VA27/10 (Consejería de Sanidad, Junta de Castilla y León).Peer Reviewe