NRAS mutant E132K identified in young-onset sporadic colorectal cancer and the canonical mutants G12D and Q61K affect distinct oncogenic phenotypes.

摘要: Recent data show a global increase in colorectal cancer (CRC) cases among younger demographics, which portends poorer prognosis. The cause of rising incidence is uncertain, and its mutational landscape remains largely unexplored, including those genes the epidermal growth factor receptor pathway. Among these are NRAS mutants where there paucity functional studies compared to KRAS. Here, novel mutant E132K, identified three tumor samples from Filipino young-onset, sporadic patients, was investigated for effects on different hallmarks, alongside canonical G12D Q61K yet poorly characterized context CRC. E132K resistance apoptosis, cytoskeletal reorganization, loss adhesion. In contrast activating KRAS mutations, analogous all have no apparent effect cell proliferation motility. results highlight need characterize isoform- mutation-specific oncogenic phenotypes can repercussions disease management choice therapeutic intervention. Further analyses young-onset versus late-onset CRC datasets necessary qualify as biomarker subtype.