Novel genetic and epigenetic alterations in ... - Ous-research.no

RESULTSMSI-analysisTumors with known MSI-status were selected for inclusion in the test set of carcinomas. Toensure a uniform MSI threshold both in the test- and the validation set, all samples were reanalyzedusing consensus markers. After re-analysis, 87 tumors were included as MSI-H and7 as MSI-L. For the validation set, MSI analysis was performed on a total of 491 tumors (385right-sided and 106 left-sided primary tumors). Twenty-six percent of the right-sided tumorsdisplayed MSI-H (n = 102), 6% were MSI-L (n = 24), 61% were MSS (n = 233) and 7%were unsuccessful (n = 26). Among the left-sided tumors, 6% were MSI-H (n = 6), 9% wereMSI-L (n = 10), 79% MSS (n = 84) and 6% unsuccessful (n = 6). In total, 108 (22%) of thetumors displayed a high degree of microsatellite instability, and were included in furtheranalyses.Mutation frequenciesMutation frequencies of the 41 genes varied from 6% (ZMYND8) to 91% (ACVR2A) witha median of 17 (range 0-28) mutated genes per sample for the MSI-H tumors in the testseries, and one (range 0-14) mutated gene per sample for the MSI-L tumors.In the validation series, mutation frequencies for each gene varied from 4% (EP300) to 92%(ACVR2A) with a median of 19 (range 0-29) mutated genes per sample. Gene specificmutation frequencies in the two tumor series can be seen in Figure 1, in which resultssummarized from the literature (from [10]) are included as well.10