Abstract 2114: Deletions/Duplications detection by MLPA in Chilean families with hereditary colorectal cancer: Lynch syndrome and FAP

Abstract

Abstract The main variants of colorectal cancer hereditary are Familial Adenomatous Polyposis (FAP) and Lynch Syndrome, which account for approximately 5% of total cases of colorectal cancer. Point mutations in APC and MMR genes are responsible of about 85% and 50% of Chilean FAP (classic phenotype) and Lynch Syndrome (Amsterdam criteria) families, respectively. Different molecular strategies are available for the detection of mutations in these genes. Studies in other populations have identified deletions and duplications of one or more consecutive exons account for around 50% and 10-20% of the total alterations in MMR and APC genes, respectively. The aim of our work was the detection of genomic deletion/duplication through Multiplex Ligation-Dependent Probe Amplification (MLPA) in Lynch Syndrome and FAP patients in Chile. In this study, we analized alterations in MLH1 and MSH2 in 26 Lynch Syndrome families (5 Amsterdam and 21 Bethesda families), and in APC in 10 FAP families (6 classic and 4 attenuated), all of them non carriers of point mutations in these genes. We identified 3 different alterations in the MLH1 in four Amsterdam families, all of them are 0.5 times deletion, which are located: exon 1 in one family, exon 19 in two families, and exons 14 and 15 in one family. In the MSH2, in one Amsterdam family we detected a 0.5 time deletion of exon 2. In the APC, we found 2 different alterations in three classic FAP families: in one family we detected a 0.5 times deletion of the whole gene including promoter region, and in two families we found a 1.5 time amplification of exons 1, 2 and 3. These alterations were confirmed in other relatives of these families and in two independent MLPA analysis. The deletion of exon 19 in MLH1 and the amplification of exons 1, 2 and 3 in APC have not been previously described in other populations. In conclusion, genomic deletions/duplications were only detected in 5 Lynch Syndrome families that fulfilled Amsterdam criteria, and in 3 FAP families with classic phenotype. The detection of different mutations involved in these syndromes, allows the development of prevention strategies of these diseases. Financed by Cleveland Clinic Foundation and Las Condes Clinic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2114.