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Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers.

12097267

Cancer Res.. 2002 Jul 62 (13).

Microsatellite instability (MSI) within coding regions causes frameshift mutations (FSMs). This type of mutation may inactivate tumor suppressor genes in cancers with frequent MSI (MSI-H cancers). To identify novel FSMs in gastric carcinogenesis in an unbiased and comprehensive manner, we screened for this type of mutation at 154 coding region repeat loci in 18 MSI-H gastric cancers. We also compared FSM rates and spectra in MSI-H gastric versus colorectal cancers. Thirteen novel loci showed FSMs in >20% of gastric tumors. Novel loci with the highest mutation frequencies included the activin type 2 receptor gene (44.4%), DKFZp564K112 (a homologue of the Drosophila tumor suppressor gene multi-sex-combs; 41.2%), and an endoplasmic reticulum chaperone protein gene SEC63 (37.5%). The mutational spectra for genes with high mutation frequencies were also significantly different between MSI-H gastric and colorectal cancers.

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