MLH1 and MSH2 mutation screening in HNPCC families of Hungary - Two new MMR gene mutations.

Abstract Introduction Hereditary Non-Polyposis Colorectal Cancer is an inherited disease with deleterious germline mutations in the DNA mismatch repair genes causing the development of colon cancer and other malignancies. This is the first study in Hungary screening the population of our colorectal cancer patients in order to identify the prevalence of the disease. Methods In families who met the Modified Amsterdam and Bethesda Criteria the removed tumor tissue was first examined by immunohistochemistry and microsatellite instability analysis. Those cases which showed high microsatellite instability underwent DNA sequencing and multiple ligation dependent probe amplification. Results Of the 1576 patients with colorectal cancer underwent screening for the modified Amsterdam and Bethesda criteria, 69 (4.4%) and 166 (10.5%) fulfilled the criteria respectively. 15 patients (31%) of the Amsterdam positive group and 19 patients from the Bethesda positive (18.1%) were MSI-H. There were 8 pathogenic mutations identified in 9 families (60%) in the Amsterdam positive group. 5 mutations were found in 5 families (26%) in the Bethesda positive group. 12 pathogenic mutations were identified, two of these are newly identified, and being published first in this work. These two new mutations were located on MLH1 (g.31276_35231del) and MSH2 (c.969_970delTC) genes. Conclusion The prevalence of the mutations in the MLH1 and MSH2 genes was almost equal in our Hungarian colorectal cancer patients. One mutation in the MLH1 gene (c.143A > C; p.Q48P) was identified in three different families. Whether this mutation is the most frequent in the Hungarian population is still unidentified and warrant further investigation.