hMLHl and hMSH2 somatic inactivation mechanisms in sporadic colorectal cancer patients

Pathology & Oncology Research

Enikó Kámory¹  Orsolya Csuka¹  Orsolya Kolacsek¹  Szabolcs Ottó¹ 

[1] National Institute of Oncology$$

关键词: promoter hypermethylation;    and inactivation;   

DOI  :  10.1007/BF02893384

学科分类：生理学与病理学

来源: Springer

【 摘 要 】

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 hMLHl and hMSH2 genes were shown to have a great importance, and in order to examine the somatic inactivation mechanisms of the two MMR genes hMLHl and hMSH2 we screened 37 Hungarian sporadic colorectal cancer patients for allelic imbalance (AI), microsatellite instability (MSI), hMLHl 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 hMLHl and hMSH2 genes, respectively. Seven tumours (19%) showed dense promoter hypermethylation of hMLHl, 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 hMLHl promoter hypermethylation which may have a role in the carcinogenesis of sporadic colorectal cancer.

【 授权许可】

Unknown