Validation and genomic interrogation of the MET variant rs11762213 as a predictor of adverse outcomes in clear cell renal cell carcinoma

BACKGROUND The exonic single‐nucleotide variant rs11762213 located in the MET oncogene has recently been identified as a prognostic marker in clear cell renal cell carcinoma (ccRCC). This finding was validated with The Cancer Genome Atlas (TCGA) cohort, and the biologic implications were explored. M...

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Veröffentlicht in:Cancer 2016-02, Vol.122 (3), p.402-410
Hauptverfasser: Hakimi, A. Ari, Ostrovnaya, Irina, Jacobsen, Anders, Susztak, Katalin, Coleman, Jonathan A., Russo, Paul, Winer, Andrew G., Mano, Roy, Sankin, Alexander I., Motzer, Robert J., Voss, Martin H., Offit, Kenneth, Purdue, Mark, Pomerantz, Mark, Freedman, Matthew, Choueiri, Toni K., Hsieh, James J., Klein, Robert J.
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Sprache:eng
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Zusammenfassung:BACKGROUND The exonic single‐nucleotide variant rs11762213 located in the MET oncogene has recently been identified as a prognostic marker in clear cell renal cell carcinoma (ccRCC). This finding was validated with The Cancer Genome Atlas (TCGA) cohort, and the biologic implications were explored. METHODS The genotype status for rs11762213 was available for 272 patients. Paired tumor‐normal data, genomic data, and clinical information were acquired from ccRCC TCGA data sets. Cancer‐specific survival (CSS) was analyzed with the competing risk method, and Cox proportional hazards regression was used for the analysis of the time to recurrence (TTR). Multivariate competing risk models were fitted to adjust for the validated Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score. RESULTS The variant allele of rs11762213 was detected in 10.3% of the cohort. After adjustments for the SSIGN score, the risk allele remained a significant predictor for adverse CSS (hazard ratio [HR], 3.88; 95% confidence interval [CI], 1.99‐7.56; P 
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.29765