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01.09.2010

Analysis of mismatch repair gene mutations in Turkish HNPCC patients

verfasst von: Berrin Tunca, Monica Pedroni, Gulsah Cecener, Unal Egeli, Enrica Borsi, Abdullah Zorluoglu, Carmela Di Gregorio, Tuncay Yilmazlar, Omer Yerci, Maurizio Ponz de Leon

Erschienen in: Familial Cancer | Ausgabe 3/2010

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Abstract

Hereditary 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.

Turkish Ministry of Health (1999) http://www.saglik.gov.tr

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Titel: Analysis of mismatch repair gene mutations in Turkish HNPCC patients
verfasst von: Berrin Tunca
Monica Pedroni
Gulsah Cecener
Unal Egeli
Enrica Borsi
Abdullah Zorluoglu
Carmela Di Gregorio
Tuncay Yilmazlar
Omer Yerci
Maurizio Ponz de Leon
Publikationsdatum: 01.09.2010
Verlag: Springer Netherlands
Erschienen in: Familial Cancer / Ausgabe 3/2010
Print ISSN: 1389-9600
Elektronische ISSN: 1573-7292
DOI: https://doi.org/10.1007/s10689-010-9336-7

Springer Medizin

Analysis of mismatch repair gene mutations in Turkish HNPCC patients

Abstract

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