ELOC – Clear Cell Renal Carcinoma

Recent studies have noted a potential association between alterations in ELOC (HGNC:11617) and clear cell renal carcinoma (MONDO_0005005). Several reports indicate that disruption of the normal function of ELOC, a component of the VCB-CR complex, may contribute to dysregulated hypoxia‐inducible factor (HIF) signaling in affected renal tissues (PMID:28667082).

In a notable case report, a patient with progressive clear cell renal carcinoma exhibited a robust response to HIF2α inhibitors, implying that aberrations in genes interacting with the VHL pathway, including ELOC, could have diagnostic and therapeutic implications (PMID:28667082). Although the number of unrelated probands documented is limited, this observation raises the possibility of an underlying genetic contribution from ELOC.

Additional multi-patient studies have evaluated the molecular profiles of various renal cell carcinomas, with ELOC recurrently listed among candidate genes. While detailed segregation data are not available and the number of probands remains low, the repetition of ELOC in these studies supports a tentative connection with clear cell renal carcinoma (PMID:34512202).

Genetic evidence is currently sparse. The reported candidate variant, c.236A>G (p.Tyr79Cys), meets HGVS criteria and, while primarily described in the context of von Hippel-Lindau disease, underscores the functional importance of ELOC in oxygen sensing and tumorigenesis. However, its direct association with clear cell renal carcinoma remains limited by insufficient segregation data (PMID:35323939).

Functional assays have provided moderate support for the role of ELOC in disease pathology. In vitro binding studies using synthetic peptides have delineated critical interactions between elongin C and other components of the VCB-CR complex, linking impaired binding to deregulated HIF signaling—a central mechanism in clear cell renal carcinoma pathogenesis (PMID:10587522).

In summary, while both genetic and functional data suggest that ELOC may be involved in the pathogenesis of clear cell renal carcinoma, the current evidence is limited due to small proband numbers and a lack of extensive segregation analysis. Further research is warranted to solidify this association, which could offer significant clinical utility in diagnostic decision‑making and personalized therapeutic strategies.

References

• Endocrine‑related cancer • 2017 • New HIF2α inhibitors: potential implications as therapeutics for advanced pheochromocytomas and paragangliomas PMID:28667082
• Pathology oncology research • 2021 • Clear Cell Papillary Renal Cell Carcinoma Shares Distinct Molecular Characteristics and may be Significantly Associated With Higher Risk of Developing Second Primary Malignancy PMID:34512202
• The Journal of clinical investigation • 1999 • Synthetic peptides define critical contacts between elongin C, elongin B, and the von Hippel-Lindau protein PMID:10587522

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