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

When comparing our findings of mutation frequencies with literature, we saw thatACVR2A, OGT and RAD50 had a higher mutation rate in our analyses, while ADCY2,EP300, PA2G4 and SEC63 were less frequently mutated as compared to the literature. Mostof these genes have been the subject of few or single studies, often with a very restrictedsample size, and therefore discrepancies were not unexpected. In the instance of ACVR2Aanother study has found a similarly high mutation frequency.[25] To the best of ourknowledge, this is the first study to analyze indels in EP300 in primary tumors. Previously ithas been shown to be mutated in 4 of 7 CRC cell lines.[26] The low mutation frequency seenhere indicates that it is not among the driving forces in colorectal tumorigenesis.Some genes showed more than a 10% difference in mutation frequency between the twotumor series (AIM2, ASTE1, EP300, EPHB2, MARCKS, PCNXL2, RBBP8, RCC2,SEMG1, SPINK5 and SYCP1). There may be biological as well as technological explanationsfor this discrepancy. Firstly, some biological variation is expected. Also, the fact that the testseries includes a higher number of non-right-sided tumors makes us expect the mutationfrequencies to be slightly lower. In fact, when comparing only right-sided tumors themutation frequencies in the two series were more similar as only SPINK5 and EP300 weresignificantly different. All of the differently mutated genes were more often mutated in theformalin fixed validation series. It may be that the tissue fixation protocol plays a part in theelevated mutation frequencies.Correlation analysis indicated that ACVR2A:TGFBR2, TAF1B:ASTE1, TAF1B:ACVR2A,and MRE11A:ASTE1 were correlated in the test series, of which the pairs of TAF1B:ACVR2A and MRE11A:ASTE1 were confirmed in the validation series. All these genes19