Clinicopathologic characteristics related to the high variability of coding mononucleotide repeat sequences in tumors with high-microsatellite instability (original) (raw)

Oncology Reports, 2003

Abstract

Frameshift mutation at coding mononucleotide repeat sequences are common in tumors with microsatellite instability (MSI-H), but the incidences are different among the target genes. We analyzed the mutational profiles of 12 known target genes containing polydeoxyadenosine repeats in their coding sequences in 39 MSI-H colorectal carcinomas and 40 MSI-H gastric carcinomas by using polymerase chain reaction and sequencing, and compared the results with the clinicopathologic characteristics. Frameshift mutations of target genes in the MSI-H colorectal and gastric carcinomas are increased according to the length of the polydeoxyadenosine repeats in the target genes. The mean mutational rates of MSI-H colorectal carcinomas and MSI-H gastric carcinomas were 2.03 and 1.95 in the 4 genes containing (A)10 repeats, 1.23 and 0.73 in the 4 genes with (A)9 repeats and 0.61 and 0.48 in the 4 genes containing (A)8 repeats, respectively (p<0.001). Among the evaluated clinicopathologic findings, intestinal type gastric carcinomas had more frameshift mutations than the diffuse type carcinomas (3.5 vs. 1.9, p=0.01). These findings suggest that mutational rates of the target genes in MSI-H tumors are diverse, and higher mutational rates are related to the length of mononucleotide repeat sequences of the target genes and histologic type of tumors.

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