RAS mutation is the most frequent oncogenic alteration in human cancers. KRAS is the
most frequently mutated followed by NRAS. The emblematic KRAS mutant cancers are pancreatic,
colorectal, lung adenocarcinomas and urogenital cancers. KRAS mutation frequencies
are relatively stable worldwide in various cancer types with the one exception of
lung adenocarcinoma. The frequencies of KRAS variant alleles appears cancer type specific,
reflecting the various carcinogenic processes. In addition to point mutation KRAS,
allelic imbalances are also frequent in human cancers leading to the predominance
of a mutant allele. KRAS mutant cancers are characterized by typical, cancer-type-specific
co-occurring mutations and distinct gene expression signatures. The heterogeneity
of KRAS mutant primary cancers is significant, affecting the variant allele frequency,
which could lead to unpredictable branching development in metastases. Selection of
minute mutant subclones in the primary tumors or metastases during target therapies
can also occur frequently in lung or colorectal cancers leading to acquired resistance.
Ultrahigh sensitivity techniques are now routinely available for diagnostic purposes,
but the proper determination of mutant allele frequency of KRAS in the primary or
metastatic tissues may have larger clinical significance.
