Study reveals potentially prognostic gene, metabolism changes in kidney cancers

Kidney tissue

Stained kidney tissue
Photo Credit: Tom Deerinck and Mark Ellisman, National Center for Microscopy and Imaging Research

The Cancer Genome Atlas Research Network investigators, including CCR scientists, identified genetic and metabolic pathway changes linked to reduced survival of patients within and across subtypes of renal cell carcinoma (RCC), a type of kidney cancer. These distinct changes demonstrate a need for the development of subgroup-specific treatment strategies. The study, published April 5, 2018, in Cell Reports, is part of The Cancer Genome Atlas (TCGA) Program, a joint effort of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI).

RCC is not one disease but rather a collection of cancers originally defined by histology, or how the cells look under a microscope. The three major subtypes are clear cell, papillary and chromophobe, and each has different driver mutations, prognoses and treatment responses. However, physicians have observed that even patients whose tumor cells look similar can have very different disease courses and outcomes.

To catalog the differences between RCC subtypes and to discover pathways that might be altered in multiple subtypes, a research team led by W. Marston Linehan, M.D., Chief of CCR’s Urologic Oncology Branch, W. Kimryn Rathmell, M.D., Ph.D., Chair of the Department of Medicine at Vanderbilt University School of Medicine, and Paul T. Spellman, Ph.D., Professor of Molecular & Medical Genetics at Oregon Health & Science University, performed a comprehensive molecular analysis of 843 histologically verified RCC tumors.

The study showed that changes in the genes BAP1, PBRM1 and PTEN as well as certain altered metabolic pathways were associated with decreased patient survival in specific RCC subtypes. Interestingly, the researchers found that changes to the gene CDKN2A, increases in a DNA modification called hypermethylation and increases in an immune expression signature called Th2 correlated with reduced patient survival in all the major subtypes. The investigators also identified a small subgroup of patients with chromophobe RCC, described as metabolically divergent, who had extremely poor survival.

Together these results demonstrate the importance of using histology and genomics to identify and to design more precise therapies for the various types of RCC.

Summary Posted: 04/2018