SAN FRANCISCO, CA USA (UroToday.com) - Previously, it has been shown that a single nucleotide polymorphism (SNP) in the coding region of the receptor MET correlated risk of recurrence in renal cell carcinoma (RCC) patients. This finding was validated and extended by A. Ari Hakimi, MD and his research group.
They used data from 331 patients in The Cancer Genome Atlas (TCGA) to show that the SNP was present in 10% of the patients and that it predicted a hazard ratio (HR) of 3.9 for cancer-specific survival and HR of 3 for time-to-recurrence. SNP analysis increased the c-index of the Mayo SSIGN prognostic nomogram, which is currently used to predict these events. The group evaluated all SNPs available in the TCGA data set and showed that no other SNP was predictive. Additionally, nearby SNPs, which might show linkage disequilibrium, were also shown to not correlate with disease outcome in a separate cohort using ENCODE data. They showed that the SNP does not correlate with mRNA or protein expression, copy number variation, or DNA hypermethylation in the TCGA dataset. This suggests that the functional significance of this SNP may be related to differences in receptor biology, or potentially differences in mRNA turnover.
Dr. Hakimi suggested that this should be incorporated into routine practice to better assess risk in this patient population because it is easily measured using a buccal swab or blood test.
Highlights of a presentation by A. Ari Hakimi, MD at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
Memorial Sloan Kettering Cancer Center, New York, NY USA