News Release

To view the TCGA papillary renal cell carcinoma findings in The New England Journal of Medicine, click here.

Thursday, November 4, 2015
5 p.m. EST

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Improved understanding of the genetic drivers of papillary renal cell carcinoma

A comprehensive genomic analysis of 161 tumors from people with papillary renal cell carcinoma (PRCC) – the second most common form of kidney cancer –provided insights into the molecular basis of this cancer and may inform its classification and treatment. PRCCs are divided into two main subtypes, Type 1 and Type 2, which are traditionally defined by how the tumor tissue appears under a microscope. Findings from this genomic analysis, carried out by investigators from The Cancer Genome Atlas (TCGA) Research Network, have confirmed that these subtypes are distinct diseases distinguished by certain genomic characteristics. This molecular information could be important in managing patients clinically, identifying new therapies, and designing clinical trials.

The researchers found that Type 1 PRCC is characterized by alterations in cell signaling involving the MET gene that are known to drive cancer cell growth, the growth of tumor blood vessels, and cancer metastasis or spread. MET gene mutations or other alterations that affect its activity were identified in 81 percent of Type 1 PRCCs examined. This finding suggests that it may be possible to treat Type 1 PRCCs with specific inhibitors of the MET cell signaling pathway, including the MET/VEGFR inhibitor foretinib, which is currently being tested in phase II clinical trials in PRCC and other cancer types. Type 2 PRCC was found to be more genomically heterogeneous. A specific characteristic, referred to as the CpG island methylation phenotype (CIMP), was found almost exclusively in Type 2 PRCC and defined a distinct Type 2 subgroup that was associated with the least favorable outcome. CIMP is marked by increased DNA methylation, which is a chemical modification of DNA that inhibits gene expression. Across all Type 2 PRCCs examined, 25 percent demonstrated decreased expression of CDKN2A, a tumor suppressor gene that helps regulate the cell cycle. Loss of CDKN2A expression was also associated with a less favorable outcome. The TCGA researchers were led by Paul Spellman, Ph.D., Oregon Health and Science University, Portland, and Marston Linehan, M.D., NCI.  Their findings were first published online November 5, 2015, in the New England Journal of Medicine. TCGA is a collaboration jointly supported and managed by the National Cancer Institute and the National Human Genome Research Institute, both part of the National Institutes of Health.