hMLH1 and hMSH2 Somatic Inactivation Mechanisms in Sporadic Colorectal Cancer Patients

Enikô KÁMORY, Orsolya KOLACSEK, Szabolcs OTTÓ, Orsolya CSUKA

Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary


Much is known about the role of germline inactivation in mismatch repair (MMR) genes in hereditary non-polyposis colorectal cancer (HNPCC), but the impact of somatic MMR gene changes on sporadic colorectal cancer remains to be elucidated. In hereditary cases the hMLH1 and hMSH2 genes were shown to have a great importance, and in order to examine the somatic inactivation mechanisms of the two MMR genes hMLH1 and hMSH2 we screened 37 Hungarian sporadic colorectal cancer patients for allelic imbalance (AI), microsatellite instability (MSI), hMLH1 promoter hypermethylation and somatic mutations. Thirteen of the examined tumours (35%) were characterized by low-level MSI and none of the cases belonged to the high MSI group. Nine (24%) and seven (19%) cases had AI at the hMLH1 and hMSH2 genes, respectively. Seven tumours (19%) showed dense promoter hypermethylation of hMLH1, but only two patients had somatic mutations, one for each MMR gene. According to our study on this limited set of cases the most prominent mismatch repair inactivation mechanism in sporadic colorectal cancer patients is the hMLH1 promoter hypermethylation which may have a role in the carcinogenesis of sporadic colorectal cancer. Pathology & Oncology Research, Vol 9, Nr 4, 236-241, 2003

Key words: sporadic colorectal cancer; mismatch repair; hMLH1; hMSH2; microsatellite instability; allelic imbalance; promoter hypermethylation and inactivation

Received: Nov 7, 2003; accepted: Nov 20, 2003
Correspondence: Orsolya CSUKA, Department of Pathogenetics, National Institute of Oncology, Rath Gyorgy u. 7-9. Budapest H-1122, Hungary, Fax: +36-1-2248775; E-mail:

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