title: The mutational spectrum of Lynch syndrome in cyprus.
abstract: Lynch syndrome is the most common form of hereditary colorectal cancer and is caused by germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Mutation carriers have an increased lifetime risk of developing colorectal cancer as well as other extracolonic tumours. The aim of the current study was to evaluate the frequency and distribution of mutations in the MLH1, MSH2 and MSH6 genes within a cohort of Cypriot families that fulfilled the revised Bethesda guidelines. The study cohort included 77 patients who fulfilled at least one of the revised Bethesda guidelines. Mutational analysis revealed the presence of 4 pathogenic mutations, 3 in the MLH1 gene and 1 in the MSH2 gene, in 5 unrelated individuals. It is noted that out of the 4 pathogenic mutations detected, one is novel (c.1610delG in exon 14 of the MLH1) and has been detected for the first time in the Cypriot population. Overall, the pathogenic mutation detection rate in our patient cohort was 7%. This percentage is relatively low but could be explained by the fact that the sole criterion for genetic screening was compliance to the revised Bethesda guidelines. Larger numbers of Lynch syndrome families and screening of the two additional predisposition genes, PMS2 and EPCAM, are needed in order to decipher the full spectrum of mutations associated with Lynch syndrome predisposition in Cyprus.
authors.affiliation: Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Loizidou
authors.affiliation: Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Neophytou
authors.affiliation: Departments of Medical and Radiation Oncology, Bank of Cyprus Oncology Center, Nicosia, Cyprus.
authors.forename: Demetris
authors.initials: D
authors.lastname: Papamichael
authors.affiliation: Departments of Medical and Radiation Oncology, Bank of Cyprus Oncology Center, Nicosia, Cyprus.
authors.forename: Panteleimon
authors.initials: P
authors.lastname: Kountourakis
authors.affiliation: Departments of Medical and Radiation Oncology, Bank of Cyprus Oncology Center, Nicosia, Cyprus.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Vassiliou
authors.affiliation: Departments of Medical and Radiation Oncology, Bank of Cyprus Oncology Center, Nicosia, Cyprus.
authors.forename: Yiola
authors.initials: Y
authors.lastname: Marcou
authors.affiliation: Departments of Medical and Radiation Oncology, Bank of Cyprus Oncology Center, Nicosia, Cyprus.
authors.forename: Eleni
authors.initials: E
authors.lastname: Kakouri
authors.affiliation: Department of Oncology, Nicosia General Hospital, Nicosia, Cyprus.
authors.forename: Georgios
authors.initials: G
authors.lastname: Ioannidis
authors.affiliation: Department of Oncology, Limassol General Hospital, Limassol, Cyprus.
authors.forename: Chrystalla
authors.initials: C
authors.lastname: Philippou
authors.affiliation: Clinical Genetics Department, Makarios III Hospital and The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Elena
authors.initials: E
authors.lastname: Spanou
authors.affiliation: Clinical Genetics Department, Makarios III Hospital and The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: George A
authors.initials: GA
authors.lastname: Tanteles
authors.affiliation: Clinical Genetics Department, Makarios III Hospital and The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Violetta
authors.initials: V
authors.lastname: Anastasiadou
authors.affiliation: Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hadjisavvas
authors.affiliation: Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Kyriacos
authors.initials: K
authors.lastname: Kyriacou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D003535:Cyprus / Q000453:epidemiology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein