WDR17 – Colorectal Cancer

This summary describes the limited evidence linking WDR17 to colorectal cancer. In a recent study, epigenetic profiling in a single patient with >150 laterally spreading tumors and a sigmoid colon cancer (PMID:36478906) identified abnormal methylation of CpG island promoters at several loci, including WDR17. Although the study also evaluated other genes, WDR17 was consistently found to be methylated in both non‐cancerous and cancerous lesions, suggesting a potential epigenetic contribution to tumorigenesis.

The overall clinical validity of the WDR17–colorectal cancer association is currently classified as Limited. This rating is supported by evidence from a single case report, representing 1 proband (PMID:36478906), without demonstration of familial segregation or recurrent sequence variants. The genetic data are confined to epigenetic alterations rather than canonical pathogenic mutations, which limits robust interpretation of causality.

Genetic evidence for WDR17 in this context is sparse. No pathogenic coding variants were reported for WDR17 in the provided study; the association relies solely on the observed promoter methylation. The inheritance mode in classical colorectal cancer predisposition is typically autosomal dominant; however, in this instance, the evidence reflects a somatic epigenetic event rather than a germline alteration, reducing the strength of genetic support.

Functional investigations of WDR17 in unrelated malignancies have revealed potential roles in oncogenesis. For example, independent studies in peripheral T‑cell lymphoma (PMID:26536348) have demonstrated that alterations in WDR17 can occur in a tumorigenic context. Nonetheless, no colorectal cancer–specific functional studies have been performed, and the mechanistic link between WDR17 methylation and colorectal tumorigenesis remains to be fully defined.

There is conflicting evidence in that functional assessments in other cancers do not directly validate a colorectal role for WDR17. Furthermore, the evidence is limited to a single patient’s epigenetic profile and lacks replication across multiple families or cohorts. As such, while the epigenetic finding is intriguing, it does not yet meet the threshold for a definitive clinical association.

In summary, the integrated evidence from genetic and functional perspectives suggests that WDR17 may be implicated in colorectal cancer through epigenetic modifications, but abundant additional validation is required. Key take‑home: Although initial data implicate WDR17 in colorectal tumorigenesis, its clinical utility as a diagnostic marker remains uncertain pending further independent genetic and functional studies.

References

• Oncology letters • 2023 • Methylation of CpG island promoters at ZNF625, LONRF2, SDC2 and WDR17 in a patient with numerous non‑granular type laterally spreading tumors and colorectal cancer: A case report PMID:36478906
• PloS one • 2015 • Concurrent Mutations in ATM and Genes Associated with Common γ Chain Signaling in Peripheral T Cell Lymphoma PMID:26536348

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