Eloc, also known as TCEB1, encodes elongin C, a key component of the VCB-CR (pVHL, elongin C, elongin B, cullin 2 and ring box 1) E3 ubiquitin ligase complex. This complex is crucial in oxygen sensing and the degradation of hypoxia-inducible factors, playing a significant role in multiple biological processes related to oxygen homeostasis [1].

In a proband with von Hippel-Lindau disease (VHL) but without a detectable VHL mutation, a de novo pathogenic variant in ELOC (NM_005648.4(ELOC):c.236A>G (p.Tyr79Cys)) was identified. This finding suggests that pathogenic ELOC variants can be a novel cause for VHL disease [1]. In renal cell carcinoma (RCC), biallelic ELOC-inactivated RCC is considered a novel subtype. Biallelic ELOC and biallelic VHL aberrations were mutually exclusive, and no mutations in TSC1, TSC2, or mTOR were identified in ELOC-mutated RCC with biallelic ELOC inactivation, supporting the classification of this as a distinct entity [2]. ELOC-mutated RCC is also recognized as a novel molecularly-defined epithelial renal tumour in the 2022 WHO classification of urogenital tumours [3,4,5,6,7].

In summary, Eloc is essential for the function of the VCB-CR E3 ubiquitin ligase complex and oxygen sensing. Research on Eloc, especially through the identification of its variants in disease models like VHL disease and RCC, has provided insights into the molecular mechanisms underlying these diseases, potentially guiding genetic testing and further understanding of tumour classification.

References:

1. Andreou, Avgi, Yngvadottir, Bryndis, Bassaganyas, Laia, Snape, Katie, Maher, Eamonn R. . Elongin C (ELOC/TCEB1)-associated von Hippel-Lindau disease. In Human molecular genetics, 31, 2728-2737. doi:10.1093/hmg/ddac066. https://pubmed.ncbi.nlm.nih.gov/35323939/

2. Batavia, Aashil A, Rutishauser, Dorothea, Sobottka, Bettina, Beerenwinkel, Niko, Moch, Holger. 2023. Biallelic ELOC-Inactivated Renal Cell Carcinoma: Molecular Features Supporting Classification as a Distinct Entity. In Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 36, 100194. doi:10.1016/j.modpat.2023.100194. https://pubmed.ncbi.nlm.nih.gov/37088333/

3. Moch, Holger, Amin, Mahul B, Berney, Daniel M, Cree, Ian, Netto, George J. 2022. The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. In European urology, 82, 458-468. doi:10.1016/j.eururo.2022.06.016. https://pubmed.ncbi.nlm.nih.gov/35853783/

4. Rizzo, Mimma, Caliò, Anna, Brunelli, Matteo, Martignoni, Guido, Camillo, Porta. 2023. Clinico-pathological implications of the 2022 WHO Renal Cell Carcinoma classification. In Cancer treatment reviews, 116, 102558. doi:10.1016/j.ctrv.2023.102558. https://pubmed.ncbi.nlm.nih.gov/37060647/

5. Alaghehbandan, Reza, Siadat, Farshid, Trpkov, Kiril. 2023. What's new in the WHO 2022 classification of kidney tumours? In Pathologica, 115, 8-22. doi:10.32074/1591-951X-818. https://pubmed.ncbi.nlm.nih.gov/36645398/

6. Mohanty, Sambit K, Lobo, Anandi, Cheng, Liang. 2022. The 2022 revision of the World Health Organization classification of tumors of the urinary system and male genital organs: advances and challenges. In Human pathology, 136, 123-143. doi:10.1016/j.humpath.2022.08.006. https://pubmed.ncbi.nlm.nih.gov/36084769/

7. Goswami, Parth R, Singh, Gyanendra, Patel, Tarang, Dave, Rushang. 2024. The WHO 2022 Classification of Renal Neoplasms (5th Edition): Salient Updates. In Cureus, 16, e58470. doi:10.7759/cureus.58470. https://pubmed.ncbi.nlm.nih.gov/38765391/