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

In order to ensure that gene mutation frequencies were not simply a function of the lengthof the microsatellite repeats, we plotted the mutation frequencies according to increasingrepeat length (Supplementary Figure). The majority of the genes (78%) have an (N)8-10repeat, and no significant increase in mutation frequency was seen. The 5 genes with an(N)11 repeat (ASTE1, MARCKS, MRE11A, PTHLH and TAF1B) were significantly morefrequently mutated compared with the remaining genes. As a whole, mutation rate is not amere consequence of repeat size, exemplified by ACVR2A, who has one of the highestmutation frequencies (91% and 92%) with only an (A)8 repeat.The overall mutation frequencies in the two tumor series and the literature were notsignificantly different from each other, as shown using Kruskal-Wallis one-way analysis ofvariance (P = 0.54). However, differences for individual genes were seen both between ourseries and the literature, as well as between the two tumor series. ACVR2A, OGT andRAD50 were more frequently mutated in our analyses as compared to the literature, whileADCY2, EP300, PA2G4 and SEC63 were less frequently mutated. EPHB2, MARCKS,PCNXL2, RBBP8, RCC2, SEMG1 and SPINK5 were more frequently mutated in thevalidation series compared to the test set.11