MLH1 and MSH2 mutation screening in HNPCC families of Hungary e Two new MMR gene mutations M. Tanyi a, * ,i , J. Olasz b,i , J.L. Tanyi c , L. T oth d , P. Antal-Szalm as e , Z. Ress f , T. Bub an f , K. Palatka f , C. Andr as g , H. Urbancsek h , Z. Garami a , O. Csuka b , L. Damjanovich a a Institute of Surgery, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary b Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary c Department of Obstetrics and Gynecology, Division of Gynecological Oncology, University of Pennsylvania, Philadelphia, USA d Pathological Department, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary e Department of Clinical Biochemistry and Molecular Pathology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary f Institute of Internal Medicine, University of Debrecen, Medical and Health Science Centre, Hungary g Oncological Department, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary h Department of Radio-Oncology, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary Accepted 11 July 2014 Available online 24 July 2014 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 immuno- histochemistry 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 pos- itive (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. Ó 2014 Elsevier Ltd. All rights reserved. Keywords: Hereditary Non-Polyposis Colorectal Cancer; Bethesda criteria; Modified Amsterdam criteria; MLH1; MSH2 Introduction Clinical presentation of HNPCC cases does not really differ from sporadic, non-familial cases. Comprehensive pedigree and molecular analysis, however, readily helps * Corresponding author. Institute of Surgery, Medical and Health Science Center, University of Debrecen, H-4032 Debrecen, M oricz Zsigmond krt. 22., Hungary. Fax: þ36 52 255 356. E-mail address: mtanyi@hotmal.com (M. Tanyi). i These two authors are equal first authors. http://dx.doi.org/10.1016/j.ejso.2014.07.032 0748-7983/Ó 2014 Elsevier Ltd. All rights reserved. Available online at www.sciencedirect.com ScienceDirect EJSO 40 (2014) 1445e1452 www.ejso.com