Molecular Characterization of Papillary Renal Cell Carcinoma Shows Differences Between Type 1 and 2 Tumors
Comprehensive molecular characterization of primary papillary renal cell carcinoma, reported in The New England Journal of Medicine by The Cancer Genome Atlas Research Network, showed that type 1 and 2 papillary renal cell carcinomas were distinct types of disease based on differences in genetic alterations and that type 2 tumors were further distinguished by subtypes associated with survival differences.
In the study, 161 primary papillary renal cell carcinomas were assessed by whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis.
Molecular Types
Type 1 tumors were associated with MET alterations. Type 2 tumors were associated with increased expression of the NRF2-antioxidant response element (ARE) pathway, CDKN2A silencing, mutation of the chromatin-modifying gene SETD2, TFE3 fusions, and a CpG island methylator phenotype (CIMP). Patients with CDKN2A alteration had significantly poorer overall survival compared with those without such alteration. CIMP, which was associated with mutation in the gene encoding fumarate hydratase, was found in a distinct subgroup of type 2 tumors and was associated with the poorest overall survival.
The investigators concluded: “Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features.”
W. Marston Linehan, MD, of the Urologic Oncology Branch of the National Cancer Institute, is the corresponding author of the article in The New England Journal of Medicine.
The study was funded by the National Institutes of Health.
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