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Low Mutation Incidence in Polymorphic Noncoding Short Mononucleotide Repeats in Gastrointestinal Cancer of the Microsatellite Mutator Phenotype Pathway¹

The Burnham Institute, La Jolla Cancer Center, La Jolla, California 92037

Frameshifts in short mononucleotide tracts (SMT) in genes, such as TGFßRII and BAX, are common in gastrointestinal tumors of the microsatellite mutator phenotype (MMP). The significance of less common mutations has been recently challenged because frequencies as high as 50% were reported in some noncoding SMTs in MMP colon cancer cell lines (L. Zhang, et al., Cancer Res., 61: 3801–3805, 2001). We did not confirm these findings after examining >50 MMP gastrointestinal cancers for mutations in eight SMT loci with the highest reported frequencies. In three of these loci, no clonal mutations were detected, and they were infrequent (2.9–6.7%) in the other five. Length polymorphisms are frequent (25.7–43.9%) in one-half of these SMTs, suggesting an explanation for the discrepancy. Because of the peculiar features of MMP tumors, low prevalence of mutations in cancer genes may not be a disqualifying criterion for their functionality.

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