Pedroni, MonicaBorsi, EnricaZorluoğlu, AbdullahDi Gregoria, CarmelaPonz de Leon, Maurizio2022-03-282022-03-282010-09Tunca, B. vd. (2010). "Analysis of mismatch repair gene mutations in Turkish HNPCC patients". Familial Cancer, 9(3), 365-376.1389-96001573-7292https://doi.org/10.1007/s10689-010-9336-7https://link.springer.com/article/10.1007/s10689-010-9336-7http://hdl.handle.net/11452/25388Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) is caused by the inheritance of a mutant allele of a DNA mismatch repair gene. We aimed to investigate types and frequencies of mismatch repair (MMR) gene mutations in Turkish patients with HNPCC and to identify specific biomarkers for early diagnosis of their non-symptomatic kindred's. The molecular characteristics of 28 Turkish colorectal cancer patients at high-risk for HNPCC were investigated by analysis of microsatellite instability (MSI), immunohistochemistry and methylation-specific PCR in order to select tumors for mutation analysis. Ten cases (35.7%) were classified as MSI (+). Lack of expression of the main MMR proteins was observed in MSI (+) tumors. Hypermethylation of the MLH1 promoter region was observed in one tumor. Nine Lynch syndrome cases showed novel germ-line alterations of the MMR gene: two frame-shifts (MLH1 c.1843dupC and MLH1 c.1743delG) and three missense mutations (MLH1 c.293G > C, MLH1 c.954_955delinsTA and MSH2 c.2210G > A). Unclassified variants were evaluated as likely to be pathogenic by using the in-silico analyses. In addition, the MSH2 c.2210G > A alteration could be considered as a founder mutation for the Turkish population due to its identification in five different Lynch syndrome families and absence in control group. The present study adds new information about MMR gene mutation types and their role in Lynch syndrome. This is the first detailed research on Turkish Lynch syndrome families.eninfo:eu-repo/semantics/closedAccessHNPCCLynch syndromeMMR genesIHCMSIMethylationMutation analysisIn-silico analysis of the unclassified variantsPre-messenger-RNASplice-site predictionCancer lynch-syndromeColorectal-cancerClinical-featuresSequence-motifsMLH1 promoterHereditaryMethylationHMLH1OncologyGenetics & heredityAdaptor proteins, signal transducingAdultAgedBase sequenceColorectal neoplasms, hereditary nonpolyposisDNA mismatch repairDNA mutational analysisFemaleFounder effectHumansImmunohistochemistryMaleMicrosatellite instabilityMiddle agedMolecular sequence dataMutationMutS homolog 2 proteinNuclear proteinsPedigreePolymerase chain reactionTumor markers, biologicalTurkeyArticle0002809221000162-s2.0-786501839763653769320373145OncologyGenetics & heredityHereditary Nonpolyposis Colorectal Cancer; Colorectal Neoplasms; Mismatch RepairBiological markerMismatch repair proteinProtein MLH1Protein MSH2AdultAgedArticleCancer riskCancer stagingClinical articleColorectal cancerControlled studyDNA methylationFemaleFrameshift mutationGene expressionGene frequencyGene mutationGenetic analysisGenetic associationGenetic riskGenetic variabilityHereditary nonpolyposis colorectal cancerHumanImmunohistochemistryMaleMicrosatellite instabilityMismatch repairMissense mutationPolymerase chain reactionPriority journalPromoter regionProtein expressionTurkey (republic)