SAN FRANCISCO—Patients with clear cell renal cell carcinoma (RCC) and the inherited exonic MET rs11762213 had a worse clinical outcome, a study presented at the 2014 Genitourinary Cancers Symposium has found.
The variant allele was an independent predictor both of adverse cancer-specific survival and time to recurrence. This suggests testing for the risk allele “could be integrated into clinical practice for prognostic stratification,” noted A. Ari Hakimi, MD, of the Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
Noting that rs11762213, located in the MET oncogene, recently was identified as a prognostic marker in clear cell RCC, the investigators used data extracted from The Cancer Genome Atlas cohort to validate this finding and explore its biologic implications in 272 patients for whom the variant call file and expression data were available.
“Overall, the variant allele of rs11762213 was detected in 10.3% of the cohort,” Dr. Hakimi stated. This was associated with a higher nuclear grade (P = 0.03), and a trend toward higher clinical stage (P = 0.07).
After adjusting for the prognostic SSIGN (Stage, Size, Grade, and Necrosis) score, they found the risk allele remained a significant predictor for adverse cancer-specific survival (P < 0.0001; odds ratio [OR], 3.88; 95% CI: 1.99-7.56) as well as time to recurrence (P = 0.003; OR, 2.97; 95% CI: 1.44-6.2).
“RNA sequencing data for MET did not reveal differences in tumor mRNA expression when stratified by risk allele, but did show differences in the normal kidney expression (P = 0.02) in a smaller cohort (n = 61),” they reported.
The risk allele is believed to influence gene expression in normal kidney tissue.
The 2014 Genitourinary Cancers Symposium is sponsored by the the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO).