LONRF2 and Colorectal Cancer

This summary evaluates the association between LONRF2 (HGNC:24788) and colorectal cancer (MONDO_0005575) based on evidence derived from a detailed case report. In the study, a comprehensive genome‑wide methylation analysis revealed that the CpG island promoter of LONRF2, among others, was hypermethylated in both laterally spreading tumor lesions and a colorectal cancer lesion, suggesting an epigenetic modification that may contribute to tumorigenesis (PMID:36478906).

The overall clinical validity of the association is currently considered to be Limited. This rating is based on evidence from a single proband report with no supportive segregation data or multiple independent validations, limiting the strength of this association despite the experimental concordance seen in the tumor methylation profiles (PMID:36478906).

From a genetic perspective, no coding pathogenic variants in LONRF2 were reported; instead, the evidence is entirely derived from epigenetic alteration. There is no report of a classic germline pathogenic sequence change such as a coding variant (e.g., no valid HGVS c. variant) in LONRF2. As such, the genetic evidence is limited by the absence of reported segregation or recurrent pathogenic variants in the literature (PMID:36478906).

Regarding the functional and experimental evidence, the study demonstrated that promoter hypermethylation of LONRF2 is present in both non‐cancerous and cancerous colonic lesions. This finding supports a potential role for LONRF2 in colorectal tumorigenesis via epigenetic regulatory mechanisms. However, additional functional assays such as gene expression studies, cellular assays, or in vivo models are needed to firmly establish a pathogenic mechanism (PMID:36478906).

There is no conflicting evidence reported to date that disputes the involvement of LONRF2 in colorectal cancer; however, the limited scope of available evidence and the single‐patient basis mean that interpretations should remain cautious. Future studies including additional patients and functional investigations will be critical to corroborate these initial findings and fully elucidate the clinical implications.

In conclusion, while the epigenetic findings linking LONRF2 promoter hypermethylation with colorectal cancer are intriguing, caution is warranted given the limited number of reports and absence of germline variant data. This evidence should be integrated with future genetic and functional studies in order to enhance diagnostic decision‑making and support potential commercial and publication activities.

Key Take‑home sentence: The emerging epigenetic evidence for LONRF2 in colorectal cancer highlights a potential regulatory role that merits further in‑depth analysis to drive clinical utility.

References

• Oncology letters • 2023 • Methylation of CpG island promoters at ZNF625, LONRF2, SDC2 and WDR17 in a patient with numerous non‑granular laterally spreading tumors and colorectal cancer PMID:36478906

Evidence Based Scoring (AI generated)