Open Access Research article

Screening of the DNA mismatch repair genes MLH1, MSH2 and MSH6 in a Greek cohort of Lynch syndrome suspected families

Georgia Thodi12, Florentia Fostira1, Raphael Sandaltzopoulos2, George Nasioulas3, Anastasios Grivas4, Ioannis Boukovinas5, Maria Mylonaki6, Christos Panopoulos7, Mirjana Brankovic Magic8, George Fountzilas109 and Drakoulis Yannoukakos1*

Author Affiliations

1 Molecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research "Demokritos", Athens, Greece

2 Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece

3 Molecular Biology Research Center HYGEIA "Antonis Papayiannis", DTCA HYGEIA, Athens, Greece

4 Department of Medical Oncology - A, Metaxa Cancer Hospital, Piraeus, Greece

5 Theagenion Cancer Hospital of Thessaloniki, Thessaloniki, Greece

6 Department of Gastroenterology, "Saint Panteleimon" General Hospital, Nikea, Greece

7 2nd Medical Oncology Department, St. Savas Regional Oncology Hospital, Athens, Greece

8 Institute of Oncology & Radiology of Serbia, Belgrade, Serbia

9 Department of Medical Oncology, Aristotle University of Thessaloniki, Papageorgiou Hospital, Thessaloniki, Greece

10 Hellenic Cooperative Oncology Group, Athens, Greece

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BMC Cancer 2010, 10:544  doi:10.1186/1471-2407-10-544

Published: 11 October 2010



Germline 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.


Forty-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.


Ten 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.


The 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.