Format

Send to

Choose Destination
Cell Rep. 2018 Sep 18;24(12):3353-3366.e5. doi: 10.1016/j.celrep.2018.08.062.

A Human Adult Stem Cell Signature Marks Aggressive Variants across Epithelial Cancers.

Author information

1
Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA 90095, USA.
2
Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA.
3
Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pathology, The First Affiliated Hospital of China Medical University, 110001 Shenyang, China.
4
Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.
5
Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA.
6
Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; Crump Institute for Molecular Imaging, UCLA, Los Angeles, CA 90095, USA. Electronic address: tgraeber@mednet.ucla.edu.

Abstract

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.

KEYWORDS:

adult stem cells; neuroendocrine prostate cancer; pan-cancer; small cell lung cancer; stem cell signature

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center