Journal
CELL REPORTS
Volume 24, Issue 12, Pages 3353-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.08.062
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Funding
- Prostate Cancer Foundation
- NIH K99/R00 Pathway to Independence award [K99CA218731]
- UCLA Medical Scientist Training Program (National Institute of General Medical Sciences [NIGMS]) [GM08042]
- NIH [1R01CA181242, 1R01CA172603, 1R01CA205001, 1U54CA217297, 1R01CA212403, 1R01CA200853, P01 CA168585]
- Department of Defense Prostate Cancer Research Program [PC150382]
- Parker Institute for Cancer Immunotherapy [20163828]
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research
- American Cancer Society [RSG-12-257-01-TBE]
- National Center for Advancing Translational Sciences UCLA Clinical and Translational Science Institute (CTSI) [UL1TR000124]
- UCLA Prostate SPORE [NIH P50CA092131]
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research-Hal Gaba Director's Fund for Cancer Stem Cell Research Award
- W.M. Keck Foundation
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Cancer progression to an aggressive phenotype often co-opts aspects of stem cell biology. Here, we developed gene signatures for normal human stem cell populations to understand the relationship between epithelial cancers and stem cell transcriptional programs. Using a pan-cancer approach, we reveal that aggressive epithelial cancers are enriched for a transcriptional signature shared by epithelial adult stem cells. The adult stem cell signature selected for epithelial cancers with worse overall survival and alterations of oncogenic drivers. Lethal small cell neuroendocrine lung, prostate, and bladder cancers transcriptionally converged onto the adult stem cell signature and not other stem cell signatures tested. We found that DNA methyltransferase expression correlated with adult stem cell signature status and was enriched in small cell neuroendocrine cancers. DNA methylation analysis uncovered a shared epigenomic profile between small cell neuroendocrine cancers. These pan-cancer findings establish a molecular link between human adult stem cells and aggressive epithelial cancers.
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