AUA 2018: ELOC-Mutated Renal Cell Carcinoma: A Distinct Clinical Entity with Unclear Disease Course

San Francisco, CA USA ( Renzo DiNatale, MD, a urology research fellow at Memorial Sloan Cancer Center, presented on hotspot mutations in ELOC and the hypothesis of how clear-cell renal cell carcinomas (RCC) with certain mutations in the ELOC gene may have an indolent disease course. He began by noting that RCC frequently has many of the same genomic mutations, but some cases of RCC, does not show the mutations typically associated with clear cell (ccRCC) or papillary RCC and instead have variations within the ELOC gene.

The authors analyzed 410 cancer genes on kidney tumor samples of 524 patients through an MSK-IMPACT gene panel. Patients with ELOC mutations were identified, separated, and had their medical records reviewed. Two genitourinary pathologists immunohistochemically stained and pathologically evaluated the tissue samples. He additionally stated that ELOC-mutant RCC has distinct pathological features that can usually signify an indolent tumor.

4 tumors with ELOC mutations were identified utilizing sequencing analysis with 100% of them demonstrating hotspot mutations and wild type VHL and PBRM1 genes. The analyzed ELOC mutations demonstrated loss of heterozygosity on chromosome 8 using copy number analysis. This loss of heterozygosity can only occur in 2 ways; chromosomal loss followed by a mutation, or a mutation preceding the loss of a chromosome. Before the study team could explore which method caused the loss of heterozygosity, they found a recent study by Mitchell et al. which timed the landmark events in the evolution of ccRCC which demonstrated that ccRCC initially lost chromosome 8, followed by the ELOC gene mutating, and lastly with additional drivers. They also explained that the reason that some samples appeared diploid at the ELOC locus was due to copy-neutral LOH. Following their treatments, 1 patient died and 2 patients developed metastasis.

In conclusion, Dr. DiNatale and team realized that ELOC-mutant RCCs are not necessarily indolent and that metastatic tumors show evolutionary trajectories of higher complexity. An audience member questioned how Mitchell et al. determined the evolutionary history and how that study could be used to infer the same timeline for ELOC-mutant RCC. Dr. Natale stated that clear cell RCC was very similar to ELOC-mutant RCC and thus could then be used to assume an analogous evolutionary history.

Presented by: Renzo DiNatale, MD

Written by: Vinay Cooper, Department of Urology, University of California-Irvine at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA