Pan-urologic cancer genomic subtypes that transcend tissue of origin

Fengju Chen, Yiqun Zhang, Dominick Bossé, Aly-Khan A. Lalani, A. Ari Hakimi, James J. Hsieh, Toni K. Choueiri, Don L. Gibbons, Michael Ittmann and Chad J. Creighton ()
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Fengju Chen: Baylor College of Medicine
Yiqun Zhang: Baylor College of Medicine
Dominick Bossé: Dana-Farber Cancer Institute
Aly-Khan A. Lalani: Dana-Farber Cancer Institute
A. Ari Hakimi: Memorial Sloan Kettering Cancer Center
James J. Hsieh: Washington University
Toni K. Choueiri: Dana-Farber Cancer Institute
Don L. Gibbons: The University of Texas MD Anderson Cancer Center
Michael Ittmann: Baylor College of Medicine
Chad J. Creighton: Baylor College of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract Urologic cancers include cancers of the bladder, kidney, prostate, and testes, with common molecular features spanning different types. Here, we show that 1954 urologic cancers can be classified into nine major genomic subtypes, on the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy number, and RNA and protein expression). Tissue dominant effects are first removed computationally in order to define these subtypes, which reveal common processes—reflecting in part tumor microenvironmental influences—driving cellular behavior across tumor lineages. Six of the subtypes feature a mixture of represented cancer types as defined by tissue or cell of origin. Differences in patient survival and in the manifestation of specific pathways—including hypoxia, metabolism, NRF2-ARE, Hippo, and immune checkpoint—can further distinguish the subtypes. Immune checkpoint markers and molecular signatures of macrophages and T cell infiltrates are relatively high within distinct subsets of each cancer type studied. The pan-urologic cancer genomic subtypes would facilitate information sharing involving therapeutic implications between tissue-oriented domains.

Date: 2017
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DOI: 10.1038/s41467-017-00289-x

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