Assessment of mutation probabilities of KRAS G12 missense mutants and their long-timescale dynamics by atomistic molecular simulations and Markov state modeling
Fig 1
The occurrences of specific KRAS G12X mutations vary among different tissues, and tissues exhibit individual preference in mutation type and position.
The occurrence of specific mutations in (A) all tissues, (B) the pancreas, (C) the large intestine, (D) the lung, (E) the peritoneum, (F) the small intestine, (G) the biliary tract, (H) the endometrium, and (I) the ovary. Numbers shown in panels B-I indicate the numbers of observed positive tumor samples. In panels B-I, the data are ordered from the highest occurrence (%) of a G12X mutation (panel B) to the lowest (panel I). Data have been collected from the COSMIC database [2] v.79 (http://cancer.sanger.ac.uk/cosmic/). (J) KRAS G12X single point mutations occur if c.34 or c.35 is mutated. (K) Mutation types observed in all tissues, the pancreas, the large intestine, and the lung. (L) Fraction of position c.35G mutations compared to all the mutations averaged over all tissues, and found in individual tissues. (M) Positional mutation preference of specific mutation types in c.34 and c.35. (N-P) Position mutation preference characterized through c.35G over c.34G in specific tissues with (N) G>A, (O) G>C, and (P) G>T mutations. Tissues with less than 50 positive samples (the peritoneum, the small intestine) have been omitted from the panels O and P. Statistically significant differences in the panels K-M compared to other tissues or position are indicated with an asterisk, * P<0.001; † = non-significant (Fischer exact test).