Reclassification of kidney cancer into nine subtypes

Reclassification of kidney cancer into nine subtypes

Researchers analyzed close to 900 kidney cancers at the molecular level and discovered that what have historically been considered three major types of kidney cancer according to their characteristics under the microscope, could be further distinguished into nine major subtypes through molecular analyses. Each subtype was unique in terms of altered molecular pathways and patient survival. 

Site of origin within the nephron was one major determinant in the classification, reflecting differences among clear cell, chromophobe, and papillary renal cell carcinomas (RCC).

Widespread molecular changes associated withTFE3 gene fusion or chromatin modifier genes were present within a specific subtype and spanned multiple subtypes.

Differences in patient survival and in alteration of specific pathways (including hypoxia, metabolism, MAP kinase, NRF2-ARE, Hippo, immune checkpoint, and PI3K/AKT/mTOR) could further distinguish the subtypes. Immune checkpoint markers and molecular signatures of T cell infiltrates were both highest in the subtype associated with aggressive clear cell RCC.

The findings are important because they help pave the way toward more effective personalized medicine. Each kidney cancer has unique characteristics. As a result, different cancers may respond differently to the same treatment. Understanding what makes each kidney cancer unique can provide clues to finding targets for effective therapies.