CRTC2 and Lung Cancer

Recent studies have identified low‐frequency somatic mutations in CRTC2 in lung cancer patients. In one study, mutations in CRTC2 were detected in 2 out of 343 sporadic lung cancer patients (PMID:24484648), with a mutation frequency of 2.5% in a separate analysis of 200 lung cancer tissues (PMID:24484648). A second study in non‑small cell lung cancer further confirmed the presence of CRTC2 alterations in 5 cases out of a cohort of NSCLC patients (PMID:25256670). These observations, although derived from relatively few affected cases, suggest a potential role for CRTC2 in lung tumorigenesis.

Genetic evidence for CRTC2 in lung cancer remains limited, given the small number of mutated cases and the lack of detailed familial segregation data. The variant c.1135C>T (p.Arg379Cys) is one of the reported alterations and serves as a representative mutation in this context. The absence of these mutations in healthy controls in both studies further supports their potential association with disease.

Functional studies conducted in colorectal cancer have demonstrated that CRTC2 phosphorylation can influence cellular proliferation, migration, and invasion (PMID:33000695). Although these experiments were performed in a different tumor type, the findings provide a mechanistic insight that may be extrapolated to support the oncogenic potential of CRTC2 alterations in lung cancer through similar deregulated signaling pathways.

There is no evidence of classical Mendelian segregation for CRTC2 mutations in lung cancer, suggesting these alterations predominantly occur in a somatic context, rather than through germline inheritance. Furthermore, while the current data do not reach the threshold for a definitive gene–disease association, the converging genetic and functional evidence across independent studies indicates that CRTC2 may contribute to lung cancer pathogenesis.

Overall, the integrated evidence supports a limited clinical validity for the association between CRTC2 and lung cancer. Additional studies, particularly those providing replication in larger cohorts and further functional characterization in lung tissue, could help clarify the role of CRTC2 mutations in lung cancer development.

Key take‑home sentence: Despite limited case numbers, the recurrent identification of CRTC2 mutations and supportive mechanistic data underscore its potential as a biomarker and therapeutic target in lung cancer.

References

• Molecular cancer • 2014 • Identification and validation of PROM1 and CRTC2 mutations in lung cancer patients PMID:24484648
• Tumour biology • 2014 • CRTC2 and PROM1 expression in non-small cell lung cancer: analysis by Western blot and immunohistochemistry PMID:25256670
• Technology in cancer research & treatment • 2020 • Phosphorylation of CREB-Specific Coactivator CRTC2 at Ser238 Promotes Proliferation, Migration, and Invasion of Colorectal Cancer Cells PMID:33000695

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