Year: 2018
Type: article
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.
Source: Cell Reports
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: U.S. Department of Defense, American Cancer Society, W. M. Keck Foundation, Prostate Cancer Foundation, Center for Outcomes Research and Evaluation, Yale School of Medicine, Parker Institute for Cancer Immunotherapy, National Institutes of Health, University of California, Los Angeles, National Institute of Mental Health, National Cancer Institute, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Clinical and Translational Science Institute, University of California, San Francisco
Awards: G1025508678, Systems Analysis of Epigenomic Architecture in Cancer Progression, G1706680303, G2159563898, G242001351, G2825120313, Overcoming BRAF-inhibitor Resistance in Melanoma, UCLA Clinical and Translational Science Institute, Histologic and Immunohistochemical Biomarkers for Heavily Treated Metastatic Prostate Cancer., Undergraduate Research Experience in Neuropsychiatric Genomics, G4455142683, UCLA-Caltech Medical Scientist Training Program, G6344221749, G6717269746, G7081889242, Role of oncogenic phosphorylated MED1 in aggressive prostate cancer, G8005472189, G8483868771, Influences of the Microenvironment on Cancer Stem Cells, G864096937, A novel strategy to identify prostate cancer biomarkers for patient management, G9000097764, Cancer Center Support Grant, Role and targeting of PRMT5 in prostate cancer
OpenAlex ID: W2892185704