Specific Genetic Alterations Observed in Papillary Renal-Cell Carcinomas

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Specific Genetic Alterations in Papillary Renal-Cell Carcinomas
Specific Genetic Alterations in Papillary Renal-Cell Carcinomas

(HealthDay News) -- Type 1 and type 2 papillary renal-cell carcinomas are characterized by specific genetic alterations, according to a study published online Nov. 4 in the New England Journal of Medicine.

W. Marston Linehan, M.D., from the National Cancer Institute in Bethesda, Md., and colleagues performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas. Whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis were conducted.

The researchers found that types 1 and 2 papillary renal-cell carcinomas were characterized by specific genetic alternations, with type 2 subclassified into three individual subtypes based on molecular differences that correlated with patient survival. MET alterations were seen in association with type 1 tumors. CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element pathway characterized type 2 tumors. A distinct subtype of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the fumarate hydratase gene exhibited a CpG island methylator phenotype.

"Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct," the authors write. "Type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features."

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