Screening of the DNA mismatch repair genes MLH1, MSH2 and MSH6in a Greek cohort of Lynch syndrome suspected families

BMC Cancer

Research Article

Christos Panopoulos¹  Maria Mylonaki²  Anastasios Grivas³  George Fountzilas⁴  Mirjana Brankovic Magic⁵  Raphael Sandaltzopoulos⁶  George Nasioulas⁷  Drakoulis Yannoukakos⁸  Florentia Fostira⁸  Georgia Thodi⁹  Ioannis Boukovinas^1,10 

[1] 2nd Medical Oncology Department, St. Savas Regional Oncology Hospital, Athens, Greece;Department of Gastroenterology, "Saint Panteleimon" General Hospital, Nikea, Greece;Department of Medical Oncology - A, Metaxa Cancer Hospital, Piraeus, Greece;Department of Medical Oncology, Aristotle University of Thessaloniki, Papageorgiou Hospital, Thessaloniki, Greece;Hellenic Cooperative Oncology Group, Athens, Greece;Institute of Oncology & Radiology of Serbia, Belgrade, Serbia;Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece;Molecular Biology Research Center HYGEIA "Antonis Papayiannis", DTCA HYGEIA, Athens, Greece;Molecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research "Demokritos", Athens, Greece;Molecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research "Demokritos", Athens, Greece;Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece;Theagenion Cancer Hospital of Thessaloniki, Thessaloniki, Greece;

关键词: Lynch Syndrome;    Pathogenic Mutation;    Amsterdam Criterion;    MSH2 Gene;    Colorectal Cancer Case;   

DOI  :  10.1186/1471-2407-10-544

 received in 2009-09-05, accepted in 2010-10-11,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundGermline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring a high relative risk of colorectal and endometrial cancer. The MLH1, MSH2 and MSH6 mutational spectrum reported so far involves minor alterations scattered throughout their coding regions as well as large genomic rearrangements. Therefore, a combination of complete sequencing and a specialized technique for the detection of genomic rearrangements should be conducted during a proper DNA-testing procedure. Our main goal was to successfully identify Lynch syndrome families and determine the spectrum of MLH1, MSH2 and MSH6 mutations in Greek Lynch families in order to develop an efficient screening protocol for the Greek colorectal cancer patients' cohort.MethodsForty-two samples from twenty-four families, out of which twenty two of Greek, one of Cypriot and one of Serbian origin, were screened for the presence of germline mutations in the major mismatch repair genes through direct sequencing and MLPA. Families were selected upon Amsterdam criteria or revised Bethesda guidelines.ResultsTen deleterious alterations were detected in twelve out of the twenty-four families subjected to genetic testing, thus our detection rate is 50%. Four of the pathogenic point mutations, namely two nonsense, one missense and one splice site change, are novel, whereas the detected genomic deletion encompassing exon 6 of the MLH1 gene has been described repeatedly in the LOVD database. The average age of onset for the development of both colorectal and endometrial cancer among mutation positive families is 43.2 years.ConclusionThe mutational spectrum of the MMR genes investigated as it has been shaped by our analysis is quite heterogeneous without any strong indication for the presence of a founder effect.

【 授权许可】

Unknown   
© Thodi et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.