M1929 Utility of MS-Mlpa Methylation Analysis in the Diagnosis of Lynch Syndrome

Despite the advances in the selection of patients for genetic testing in Lynch syndrome at least a third of patients with Bethesda criteria and lack of MLH1 expression have sporadic tumours and should not receive genetic testing. The aim of this study is to investigate the role of the methylation analysis using MS-MLPA in the diagnosis of Lynch syndrome. MSMLPA is a novel and methodologically easy technique for quantitative measure of gene methylation. Methods. Sixty colorectal cancer (CRC) specimens with loss of MLH1 expression were selected. DNA from paraffin-embedded tumours was tested for 2 quantitative methylation detection methods: Methylight (Applied biosystems) and MS-MLPA (Methylation Specific-Multiplex Ligation Probe Amplification) (MCR Holland) calculating Methylation Ratio in MLH1. Somatic mutation in BRAF V600E was investigated from tumour DNA. Germline mutations in MLH1 were analyzed by sequentiation. Results: Correlation of quantitative results of the 2 methylation analysis techniques (Methylation and MS-MLPA) was 96.7% (p