Absence of an embryonic stem cell DNA methylation signature in human cancer

Background Differentiated cells that arise from stem cells in early development contain DNA methylation features that provide a memory trace of their fetal cell origin (FCO). The FCO signature was developed to estimate the proportion of cells in a mixture of cell types that are of fetal origin and a...

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Vydáno v:BMC cancer Ročník 19; číslo 1; s. 711 - 12
Hlavní autoři: Zhang, Ze, Wiencke, John K., Koestler, Devin C., Salas, Lucas A., Christensen, Brock C., Kelsey, Karl T.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London BioMed Central 19.07.2019
BioMed Central Ltd
BMC
Témata:
Adult
Algorithms
Analysis
Biological markers
Biomarkers
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer Epigenomics
Cancer genetics
Cancer Research
Cell differentiation
Cell Plasticity
Cellular Reprogramming - genetics
CpG Islands
DNA
DNA methylation
DNA Methylation - genetics
Embryonic stem cells
Epigenesis, Genetic
Female
Gene expression
Genetic Heterogeneity
Genetic Loci
Genomes
Genomics
Health Promotion and Disease Prevention
Human embryonic stem cells
Human Embryonic Stem Cells - metabolism
Humans
Linear Models
Male
Medicine/Public Health
Methylation
Neoplasms - genetics
Neoplasms - pathology
Neoplastic Stem Cells - metabolism
Oncology
post-genomic analysis and emerging technologies
Pregnancy
Regression analysis
Research Article
Statistics, Nonparametric
Stem cells
Surgical Oncology
Systems biology
Transcriptome
Tumors
Human embryonic stem cells
DNA methylation
Biomarkers
Cancer Epigenomics
Cell differentiation
ISSN:1471-2407, 1471-2407
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Shrnutí:Background Differentiated cells that arise from stem cells in early development contain DNA methylation features that provide a memory trace of their fetal cell origin (FCO). The FCO signature was developed to estimate the proportion of cells in a mixture of cell types that are of fetal origin and are reminiscent of embryonic stem cell lineage. Here we implemented the FCO signature estimation method to compare the fraction of cells with the FCO signature in tumor tissues and their corresponding nontumor normal tissues. Methods We applied our FCO algorithm to discovery data sets obtained from The Cancer Genome Atlas (TCGA) and replication data sets obtained from the Gene Expression Omnibus (GEO) data repository. Wilcoxon rank sum tests, linear regression models with adjustments for potential confounders and non-parametric randomization-based tests were used to test the association of FCO proportion between tumor tissues and nontumor normal tissues. P -values of < 0.05 were considered statistically significant. Results Across 20 different tumor types we observed a consistently lower FCO signature in tumor tissues compared with nontumor normal tissues, with 18 observed to have significantly lower FCO fractions in tumor tissue (total n  = 6,795 tumor, n  = 922 nontumor, P  < 0.05). We replicated our findings in 15 tumor types using data from independent subjects in 15 publicly available data sets (total n  = 740 tumor, n  = 424 nontumor, P  < 0.05). Conclusions The results suggest that cancer development itself is substantially devoid of recapitulation of normal embryologic processes. Our results emphasize the distinction between DNA methylation in normal tightly regulated stem cell driven differentiation and cancer stem cell reprogramming that involves altered methylation in the service of great cell heterogeneity and plasticity.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1471-2407
1471-2407
DOI:10.1186/s12885-019-5932-6