Functional Analysis of Rare RAS Variants of Unknown Significance.

ABSTRACT: The RAS gene is frequently mutated in human cancers. Whereas the functional significance of frequent mutations is well established, the significance of rare mutations remains unknown. This study aimed to comprehensively investigate the function of rare RAS variants and provide new insights about their clinical relevance. A total of 298 K/N/HRAS variants (169, 72, and 57 variants, respectively) reported in the COSMIC database v100 were introduced into 3T3 cells. Subsequently, the drug sensitivity of KRAS variants to BI-2865, a noncovalent pan-KRAS inhibitor, was evaluated using the mixed-all-nominated-in-one method. The 3T3 focus formation assay newly identified 35 KRAS, 10 NRAS, and 21 HRAS variants as transforming competent. The oncogenicity assessed in the present study was consistent wi

SUBMITTER: Park S 

PROVIDER: S-EPMC12488390 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature