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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Smith, BA; Balanis, NG; Nanjundiah, A; Sheu, KM; Tsai, BL; Zhang, Q; Park, JW; Thompson, M; Huang, J; Witte, ON; Graeber, TG

Published Date

  • September 18, 2018

Published In

Volume / Issue

  • 24 / 12

Start / End Page

  • 3353 - 3366.e5

PubMed ID

  • 30232014

Pubmed Central ID

  • 30232014

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2018.08.062

Language

  • eng

Conference Location

  • United States