KRAS is one of the most frequently mutated oncogenes in human cancer, with significant mutation rates in common epithelial malignancies such as colon cancer (~40%), lung cancer (~20%), gastric cancer (~10%), and pancreatic cancer (~65%) (COSMIC database; http://www.sanger.ac.uk/genetics/CGP/cosmic/) [ 2, 3].
In comparison to the Wood et al.study, we also found a handful of highly mutated gene peaks, including peaks in KRAS and TP53 and significant mutation frequency in APC (Table 2).
We found significant mutation frequency in a number of genes previously known to be somatically mutated in colon cancer patients including APC, TP53 and KRAS.
Women with a clinically significant mutation in one of those genes have a 35 to 84percentt probability of developing breast cancer by age 70 and a 10 to 50percentt probability of developing ovarian cancer, far higher than for women in general.
This implies that the cytochrome c gene experienced a period of significant mutation relatively recently in the anthropoid lineage that gave rise to the four pseudogenes in class 1 only after these mutations.
Significant mutation rates (>40%) have been reported for some 8 mer repeats[16].
Supplementary Tables S1, S2, and S3 list the significant mutation clusters in the three species groups.
Only between 2% and 10% of the genes we analyze contain a statistically significant mutation cluster.
Significant mutation calling was determined from experimental noise by statistical analysis of raw data using T-test (p≤0.05).
Of tumors with apparent heterozygous deletions, one also contained a significant mutation identified by sequencing (Case 41, which harbors a 26 bp deletion, Table S1).
As the virus appeared in its most virulent form in 2006, it is expected that any significant mutation, especially in the multibasic aa sequence, should lead to lower virulence.
