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

作者：Blanco Ana; de la Hoya Miguel; Balmana Judith; Ramon y Cajal Teresa; Teule Alex; Miramar Maria Dolores; Esteban Eva; Infante Mar; Benitez Javier; Torres Asuncion; Tejada Maria Isabel; Brunet Joan; Grana Begona; Balbin Milagros; Perez Segura Pedro; Osorio Ana; Velasco Eladio A; Chirivella Isabel; Calvo Maria Teresa; Feliubadalo Lidia; Lasa Adriana; Diez Orland; Carracedo Angel; Caldes Trinidad; Vega Ana^*

来源：Breast Cancer Research and Treatment, 2012, 132(1): 307-315.

DOI：10.1007/s10549-011-1842-2

• Familial breast cancer
• PALB2
• Male breast cancer
• Genomic rearrangement
• BRCA1/BRCA2-negative families
• In silico analysis

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.

• 出版日期2012-2