495P - Contribution of Rare Germline Copy Number Variants and Single Nucleotide Polymorphisms to Familial Colorectal Cancer

Abstract

ABSTRACT Aim: Lynch Syndrome (LS) is the most common hereditary disease associated with colorectal carcinomas (CRC). Approximately 50% of cases presented mutations in mismatch repair (MMR) genes. Therefore, the molecular etiology of half of patients is still largely unknown, suggesting that other genetic or epigenetic hereditary factors might be associated with the cancer predisposition. Methods: Germline copy number variations (CNVs) were screened in 58 LS patients negative for pathogenic mutations in MMR genes, using a CGH 4x180K platform (Agilent Technologies). Genomic data were analyzed with Genomic Workbench software. A CNV data of 100 healthy Brazilian women analyzed with the same platform and parameters were used as a reference group (Krepischi et al., 2012; Breast Cancer Res 14:R24). The results were compared with the Database of Genomic Variants (DGV-hg18). The CNVs were classified as rare if detected in Results: A reduced number of CNVs in cases (263; 4.5 ± 3.6 CNVs/individual) were found in comparison with the Brazilian reference dataset (706; 7.1 ± 3.2 CNVs/individual) (Mann-Whitney Test, p Conclusions: These results suggested that patients with a proficient MMR profile, rare CNVs and SNPs might contribute to the risk of CRC development in Lynch syndrome patients. Disclosure: All authors have declared no conflicts of interest.