Validation and genomic interrogation of the MET variant @entity72027 as a predictor of adverse outcomes in XXXX .

@entity1 @entity39 @entity5 @entity14782 @entity72027 @entity1358
BACKGROUND: The exonic single-nucleotide variant @entity72027 located in the MET oncogene has recently been identified as a prognostic marker in @entity1358 ( @entity1358 ). This finding was validated with The @entity5 (TCGA) cohort, and the biologic implications were explored. METHODS: The genotype status for @entity72027 was available for 272 @entity1 . @entity5 -normal data, genomic data, and clinical information were acquired from @entity1358 TCGA data sets. @entity5 -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 @entity39 (SSIGN) score. RESULTS: The variant allele of @entity72027 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   <   .0001) and for TTR (OR, 2.97; 95% CI, 1.43-6.2; P   =   .003). The mapping of @entity72027 to regulatory regions within the genome suggested that it might affect a DNA @entity14782 region. RNA and protein sequencing data for MET did not reveal differences in steady-state expression with stratification by risk allele. CONCLUSIONS: The exonic MET variant @entity72027 is an independent predictor of adverse CSS and TTR in @entity1358 and should be integrated into clinical practice for prognostic stratification. Genomic analysis suggests that the single-nucleotide polymorphism may affect an @entity14782 region located in the coding region of MET. Further biological mechanistic interrogation is currently underway. @entity5 2016;122:402-410.    2015 American @entity5 Society.
