[Mutation analysis on MSH2 and MLH1 genes in patients of colorectal cancer at early age].

Objective: To investigate the etiological role of function and construction alteration in mismatch repair genes MSH2 and MLH1 in the patients onset of colorectal cancers (CRC) at early ages.

Methods: The genomic DNA was extracted from the tumor tissues and normal colon tissues during operation and subjected to analysis of microsatellite instability (MSI) in 42 Chinese patients aged less than 50 with CRC. Mutation screenings were performed with denaturing high-performance liquid chromatography (DHPLC) followed by DNA sequencing of DNA samples with variant peaks, and genomic deletion detection with quantitative multiplex PCR (Q-M-PCR) in the patients uncovered with MSI(+).

Results: 22 out of the 42 (52.4%) patients investigated were microsatellite instability positive (MSI(+)), 10/42 MSI(+)-H and 12/42 MSI(+)-L. 8 kinds of DNA germline alterations, 5 polymorphisms and 3 novel point mutations, were found in 9 patients with MSI(+). A large DNA (exon 1-6) deletion in MSH2 gene and a missense mutation Met242Ile in MLH1 gene were unveiled in CRC tissues of two patients with MSI(+)-H.

Conclusion: Mutations of mismatch repair genes are frequent in Chinese patients of CRC with onset at early ages.