Abstract 5599: Screening for large genomic rearrangements in the FANCA and FANCJ genes reveals extensive genomic FANCA deletion in a Finnish breast cancer family

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL A portion of familial breast cancer is accounted for by mutations in the same genes that are inactivated in Fanconi anemia (FA). In the current study we set out to evaluate the role of large genomic rearrangements in the FANCA and FANCJ/BRIP1 genes in Finnish breast cancer families. Mutations in the upstream FANCA gene account for the majority of FA patients, and about one-third of all FANCA mutations are large intragenic deletions. Based on the gene's hypermutable nature, the protein's interaction with BRCA1 and its involvement in genomic integrity maintenance, we considered FANCA as a candidate for breast cancer susceptibility. In FANCJ, which is a downstream FA and known breast cancer susceptibility gene, early truncating mutations have been reported, but no large deletions have been recognized so far. For the present study, blood DNA from affected index persons of 100 Northern Finnish breast cancer families were assessed for possible constitutional exonic deletions or amplifications in FANCA and FANCJ by using the multiplex ligation-dependent probe amplification (MLPA) method. We identified a novel large heterozygous FANCA deletion in one of the studied breast cancer families, removing the promoter region and the first 12 exons of the gene. The defective allele was absent from all of the tested 124 controls as well as 540 unselected breast cancer cases, but was present in the father of the index patient having pancreatic cancer. No large deletions in FANCJ were uncovered. We conclude that large FANCA deletions might contribute to breast cancer susceptibility, therefore more extensive studies on their involvement in the disease are needed. To our knowledge, this is the first report on the existence of a large-size genomic deletion in an upstream FA gene in association with familial breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5599. doi:10.1158/1538-7445.AM2011-5599