TY - JOUR
T1 - Pan-urologic cancer genomic subtypes that transcend tissue of origin
AU - Chen, Fengju
AU - Zhang, Yiqun
AU - Bossé, Dominick
AU - Lalani, Aly Khan A.
AU - Hakimi, A. Ari
AU - Hsieh, James J.
AU - Choueiri, Toni K.
AU - Gibbons, Don L.
AU - Ittmann, Michael
AU - Creighton, Chad J.
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85026808689&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-00289-x
DO - 10.1038/s41467-017-00289-x
M3 - Article
C2 - 28775315
AN - SCOPUS:85026808689
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 199
ER -