title: MLH1 and MSH2 mutation screening in HNPCC families of Hungary - Two new MMR gene mutations.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Surgery, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary. Electronic address: mtanyi@hotmal.com.
authors.forename: M
authors.initials: M
authors.lastname: Tanyi
authors.affiliation: Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Olasz
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecological Oncology, University of Pennsylvania, Philadelphia, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Tanyi
authors.affiliation: Pathological Department, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Tóth
authors.affiliation: Department of Clinical Biochemistry and Molecular Pathology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Antal-Szalmás
authors.affiliation: Institute of Internal Medicine, University of Debrecen, Medical and Health Science Centre, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Ress
authors.affiliation: Institute of Internal Medicine, University of Debrecen, Medical and Health Science Centre, Hungary.
authors.forename: T
authors.initials: T
authors.lastname: Bubán
authors.affiliation: Institute of Internal Medicine, University of Debrecen, Medical and Health Science Centre, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Palatka
authors.affiliation: Oncological Department, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
authors.forename: C
authors.initials: C
authors.lastname: András
authors.affiliation: Department of Radio-Oncology, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.
authors.forename: H
authors.initials: H
authors.lastname: Urbancsek
authors.affiliation: Institute of Surgery, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Garami
authors.affiliation: Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary.
authors.forename: O
authors.initials: O
authors.lastname: Csuka
authors.affiliation: Institute of Surgery, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Damjanovich
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D006814:Hungary; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D044465:White People
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: Bethesda criteria; Hereditary Non-Polyposis Colorectal Cancer; MLH1; MSH2; Modified Amsterdam criteria