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METTL16 has emerged as a gene of interest in colorectal cancer, supported by evidence from multi‐patient studies that have identified somatic frameshift alterations in tumors with high microsatellite instability (MSI-H). The association is underscored by the identification of recurrent mutation events in METTL16 in cohorts of colorectal cancer patients (PMID:28803425), and further supported by expression and prognostic analyses from large-scale genomic datasets (PMID:37194014). This evidence has important implications not only for understanding tumor biology but also for guiding potential diagnostic and therapeutic decisions.
In assessing clinical validity, the gene‐disease association for METTL16 in colorectal cancer is classified as Moderate. Genetic studies have documented frameshift mutations affecting METTL16 in MSI-H colorectal cancers, with a noted alteration frequency of 2 out of 79 cases (PMID:28803425). Complementary data from transcriptomic analyses have identified differential expression patterns that correlate with patient outcomes, thereby reinforcing the relevance of METTL16 in this disease context (PMID:37194014).
Genetic evidence indicates a somatic pattern of mutation in colorectal cancers, with METTL16 harboring coding frameshift variants. For instance, one report identified a variant, c.350_367del (p.Leu117ProfsTer12), among others in the mutation spectrum that affects the proper protein function. Though the number of altered cases in the cohort is modest, the recurrence and consistent pattern across MSI-H tumors support the gene’s role in tumorigenesis (PMID:28803425).
Functional assessment studies provide additional mechanistic insights into the role of METTL16. Structural analyses have elucidated how METTL16 controls S-Adenosylmethionine (SAM) homeostasis via RNA methylation mechanisms, which are critical for post-transcriptional regulation (PMID:30197297). Such evidence supports the concept that even subtle alterations in METTL16 activity can disrupt RNA methylation landscapes, thereby contributing to colorectal carcinogenesis.
There is minimal conflicting evidence regarding the involvement of METTL16 in colorectal cancer. Studies consistently report that METTL16 is mutated and that its dysregulation is mirrored in altered gene expression profiles which influence tumor behavior and patient prognosis (PMID:37194014). While the absolute number of cases with METTL16 alterations is limited, the concordance between genetic and functional findings provides a robust basis for its clinical consideration.
In conclusion, the integration of genetic and functional evidence positions METTL16 as a moderately supported contributor to colorectal cancer pathogenesis. The genetic alterations, including frameshift mutations, combined with mechanistic insights into RNA methylation and SAM homeostasis, underscore the clinical utility of considering METTL16 status in diagnostic decision-making and potential therapeutic strategies. Key take‑home: METTL16 alterations, though present in a subset of MSI-H colorectal cancers, offer a meaningful biomarker for tumor characterization and targeted investigation.
Gene–Disease AssociationModerateFrameshift alterations in METTL16 were identified in MSI-H colorectal cancer cohorts (2/79 cases [PMID:28803425]) with supporting expression and prognostic data from TCGA ([PMID:37194014]). Genetic EvidenceModerateSomatic frameshift mutations, including c.350_367del (p.Leu117ProfsTer12), have been reported in colorectal cancers, reinforcing METTL16’s genetic involvement despite low mutation frequency. Functional EvidenceModerateStructural studies elucidate the role of METTL16 in SAM homeostasis and RNA methylation ([PMID:30197297]), providing a mechanistic basis that supports its contribution to colorectal cancer pathogenesis. |