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Recent studies have implicated CRTC2 in non‑small cell lung carcinoma (NSCLC). In one study, exome and Sanger sequencing in a lung cancer pedigree and a larger multi‑patient cohort (n = 200) identified CRTC2 mutations in 5 NSCLC tissues (PMID:25256670). The mutation detection was supported by expression analyses showing significantly elevated CRTC2 protein levels in NSCLC tissues harboring mutations compared with controls, and the mutation findings correlated with clinical parameters such as male gender, adenocarcinoma histology, smoker status, and older age. This genetic evidence, though limited in the number of affected probands and lacking extensive segregation data, underscores a potential genetic contribution to NSCLC risk.
Moreover, functional studies in a different cancer context have provided insight into the biological role of CRTC2. In colorectal cancer cells, for example, the c.712T>G (p.Ser238Ala) alteration was shown to impair phosphorylation‐mediated regulation of CRTC2, subsequently affecting cell proliferation, migration, and invasion (PMID:33000695). Although these functional assessments were performed in colorectal cancer models, they provide a plausible mechanistic basis that may be extrapolated to NSCLC pathogenesis. Direct functional analyses in NSCLC remain to be conducted.
The observed segregation in a small lung cancer pedigree further supports the role of CRTC2 as a potential modifier in NSCLC, but the overall genetic evidence remains modest. Combined, the genetic and experimental results provide a coherent narrative linking aberrations in CRTC2 to NSCLC pathobiology. Additional studies are anticipated to clarify the exact contribution of CRTC2 mutations to NSCLC onset and progression.
Key take‑home sentence: While current evidence is limited, CRTC2 mutations and altered expression may serve as a useful biomarker in the diagnostic stratification of non‑small cell lung carcinoma.
Gene–Disease AssociationLimitedCRTC2 mutations were identified in 5 NSCLC tissues from a 200‑case cohort (PMID:25256670) and segregation in a lung cancer pedigree provides additional, albeit modest, support. Genetic EvidenceLimitedGenetic analyses detected CRTC2 mutations that correlate with adverse clinicopathological features in NSCLC, including the reported variant, supporting its putative role despite a modest number of affected probands (PMID:25256670). Functional EvidenceLimitedFunctional studies in colorectal cancer cells demonstrate that the c.712T>G (p.Ser238Ala) change alters CRTC2 activity by affecting phosphorylation and nuclear localization, suggesting an oncogenic mechanism that might extend to NSCLC (PMID:33000695). |