Two Germline Alterations in Mismatch Repair Genes Found in a HNPCC Patient with Poor Family History

Enikõ KÁMORY1, Miklós TANYI2, Orsolya KOLACSEK1, Judit OLASZ1, László TÓTH3, László DAMJANOVICH2, Orsolya CSUKA1

1Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary
21st Department of Surgery, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
3Department of Pathology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary


The Bethesda guidelines may offer more useful criteria in patients’ selection for germline mismatch repair gene mutation analysis than guidelines merely based on family background. An early onset double primary colorectal cancer patient with poor family history with MSI-H status was investigated for MLH1 promoter methylation, expression of the MLH1 and MSH2 gene by immunohistochemistry and mutations in the MLH1 and MSH2 genes. The index patient carried two germline alterations, the p.Val716Met in MLH1 and the c.2210+1G>C in MSH2 genes, and both tumors failed to express MLH1 and MSH2 proteins. After subsequent analysis of the whole family of the index patient, the p.Val716Met variant can be defined as a rare polymorphism with the possible contribution of pathogenicity to tumor formation and c.2210+1G>C as a true pathogenic mutation causing an out-of-frame deletion of exon 13. Pathology & Oncology Research, Vol 12, Nr 4, 228-233, 2006

Key words: Bethesda criteria; hereditary nonpolyposis colorectal cancer; hMLH1; hMSH2; microsatellite instability; immunohistochemistry

Received: Sep 11, 2006; accepted: Oct 21, 2006
Correspondence: Enikõ KÁMORY, Department of Pathogenetics, National Institute of Oncology, Ráth György u. 7-9. Budapest H-1122, Hungary; Tel: +36-30-3043364, Fax: +36-1-3162869; E-mail:

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