Expansion of the genotypic and phenotypic spectrum in patients with <i>KRAS</i> germline mutations

Abstract

Our findings reinforce the picture of a clustered distribution of disease associated KRAS germline alterations. We further defined the phenotypic spectrum associated with KRAS missense mutations and provided the first evidence of clinical differences in patients with KRAS mutations compared with Noonan syndrome affected individuals with heterozygous PTPN11 mutations and CFC patients carrying a BRAF, MEK1 or MEK1 alteration, respectively. We speculate that the observed phenotypic variability may be related, at least in part, to specific genotypes and possibly reflects the central role of K-Ras in a number of different signalling pathways.