The origins and genetic interactions of KRAS mutations are allele- and tissue-specific

The *KRAS* gene is often mutated at several hotspot codons in cancer, resulting in similar, yet distinct, functional impacts on the KRAS protein. Here, the authors examine the genetic interactions of the different *KRAS* mutations across multiple cancer types and discover that *KRAS* mutations have allele- and tissue-specific mutagenic origins, comutation patterns, and dependency interactions.

Tissue-specific oncogenic activity of KRAS A146T

*KRAS* is the most frequently mutated oncogene. The incidence of specific *KRAS* alleles varies between cancers from different sites, but it is unclear whether allelic selection results from biological selection for specific mutant KRAS proteins. We …