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Target Gene Mutation Profile Differs between Gastrointestinal and Endometrial Tumors with Mismatch Repair Deficiency¹

INSERM U434-CEPH, 75010 Paris, France [A. D., M. R., A. C., R. H.]; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200 Porto, Portugal [R. S.]; Department of Genetics and Microbiology, University of Pavia, 27100 Pavia, Italy [G. N. R.]; and Department of Surgery, University of Western Australia, Nedlands, 6907 Australia [B. I.]

Mutation frequencies at 25 genes containing coding repeats were comparedin colorectal, gastric, and endometrial mismatch repair-deficient (MSI-H) tumors. The overall number of mutations was significantly lower in endometrial than in gastrointestinal MSI-H cancers. Using a likelihood statistical method, target genes were divided in each tumor location into two groups likely to represent gene mutations that do or do not provide selective pressures during tumoral progression. Mutation profiles were quite similar in gastric and colorectal MSI-H cancers but were different in endometrial MSI-H tumors. Deletions in Bat-25 and Bat-26 noncoding repeats were also significantly less important in endometrial as compared with gastrointestinal MSI-H tumors. Our results show that the profile of target gene mutations in MSI-H tumors is tissue specific, with both qualitative and quantitative differences between gastrointestinal and endometrial MSI-H cancers.

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