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

ACVR2 ASTE1 CASP5 MARCKS MBD4 MRE11A MSH3 TAF1B TGFBR2Right colon (n = 22) 100 % 82 % 77 % 77 % 59 % 91 % 73 % 91 % 96 %Left colon (n = 7) 71 % 57 % 43 % 29 % 0 % 57 % 57 % 57 % 57 %Rectum (n = 7) 57 % 29 % 29 % 29 % 14 % 29 % 0 % 29 % 29 %P -value 0.008 0.028 0.038 0.015 0.007 0.004 0.003 0.004 < 0.001Table 1. Mutation frequencies at different tumor sites. All 9 genes with significantly different mutationfrequencies in MSI-H tumors from different sites in the colon are listed.Survival analysesA univariate five year disease-free survival analysis of the mutation status of the 41 genes inthe test series indicated that mutations in AXIN2 and EP300 were significantly associatedwith a worse prognosis while mutations in MRE11A, OGT and RCC2 were associated with abeneficial prognosis (Table 2 top left). The positive association between survival andmutation in RCC2 was confirmed in the validation series (Figure 4 and Table 2 bottom left).In addition, mutation in GRK4 and RBBP8 was associated with poor survival in thevalidation series (Table 2 bottom).Figure 4. Survival and RCC2 mutation. Both in the test series (left plot) and the validation series (right plot)show a significant association between mutations in RCC2 and improved survival.16