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

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31324166", "kind": "science-record", "revision": 7, "content_hash": "sha256:d4eff9045e35d07e08cae67b295adeaf16ddabc5be3ffc11a94ddd60b36cd6ca", "created_at": "2026-11-01T15:40:47Z", "updated_at": "2026-11-01T22:00:43Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Absence of an embryonic stem cell DNA methylation signature in human cancer.", "doi": "10.1186/s12885-019-5932-6", "pmid": "31324166", "authors": ["Ze Zhang", "John K Wiencke", "Devin C Koestler", "Lucas A Salas", "Brock C Christensen", "Karl T Kelsey"], "journal": "BMC cancer", "year": 2019, "abstract": "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.\nMETHODS: 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.\nRESULTS: 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).\nCONCLUSIONS: 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.", "claims": [{"id": "claim-method", "statement": "A Wilcoxon rank sum test was fit independently to each TCGA study and used to compare the predicted FCO in tumor versus nontumor normal tissue.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31324166", "locator": "sections[4] \"Comparison of predicted FCO between tumor tissue and nontumor normal tissue\" paragraph 2", "quote": "A Wilcoxon rank sum test was fit independently to each TCGA study and used to compare the predicted FCO in tumor versus nontumor normal tissue."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Availability of data and materialsThe datasets analyzed during the current study are available on The Cancer Genome Atlas (TCGA) https://portal.gdc.cancer.gov and the Gene Expression Omnibus data repository https://www.ncbi.nlm.nih.gov/geo/ (Accession numbers: GSE49656, GSE53051, GSE52068, GSE52826, GSE52955, GSE54503, GSE56044, GSE75546, GSE77871, GSE85845, GSE76938, GSE112047, GSE101961, GSE72245, GSE106600, GSE80241, GSE92462).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31324166", "locator": "sections[18] \"notes\" paragraph 1", "quote": "Availability of data and materialsThe datasets analyzed during the current study are available on The Cancer Genome Atlas (TCGA) https://portal.gdc.cancer.gov and the Gene Expression Omnibus data repository https://www.ncbi.nlm.nih.gov/geo/ (Accession numbers: GSE49656, GSE53051, GSE52068, GSE52826, GSE52955, GSE54503, GSE56044, GSE75546, GSE77871, GSE85845, GSE76938, GSE112047, GSE101961, GSE72245, GSE106600, GSE80241, GSE92462)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31324166"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6642562", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:31324166:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2a10b6e86d80b6c0395eda0a164da55ca18188faac19a03cef968ef5d6b10522", "bytes": 2329, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#Tab1", "version": null, "note": "Baseline characteristics of TCGA tumor projects included in the study", "structure": {"pmcid": "PMC6642562", "section_index": 8, "section_title": "Results", "row_count": 22, "column_count": 9}, "table": {"label": "Table 1", "caption": "Baseline characteristics of TCGA tumor projects included in the study", "rows": [["TCGA Tumor Abbreviation", "Tumor n", "Nontumor normal n", "Mean age (sd)", "Male n (%)", "White n (%)", "Black n (%)", "Asian n (%)", "Other race n (%)"], ["BLCA", "418", "21", "68.60 (10.60)", "319 (72.7)", "351 (83.6)", "25 (6.0)", "44 (10.5)", "0 (0.0)"], ["BRCA", "791", "97", "58.72 (13.34)", "9 (1.0)", "668 (76.6)", "164 (18.8)", "39 (4.5)", "1 (0.1)"], ["CESC", "307", "23", "48.77 (13.79)", "0 (0.0)", "213 (77.7)", "31 (11.3)", "20 (7.3)", "10(3.6)"], ["CHOL", "36", "9", "65.07 (12.46)", "22 (48.9)", "40 (88.9)", "2 (4.4)", "3 (6.7)", "0 (0.0)"], ["COAD", "313", "38", "66.21 (13.21)", "188 (53.9)", "240 (75.7)", "65 (20.5)", "11 (3.5)", "1 (0.3)"], ["ESCA", "185", "16", "63.41 (11.87)", "168 (83.6)", "130 (71.8)", "5 (2.8)", "46 (25.4)", "0 (0.0)"], ["GBM", "140", "140", "60.44 (12.72)", "81 (58.3)", "107 (81.7)", "24 (18.3)", "0 (0.0)", "0 (0.0)"], ["HNSC", "528", "50", "61.54 (11.82)", "424 (73.4)", "495 (88.1)", "54 (9.6)", "11 (2.0)", "2 (0.4)"], ["KIRC", "324", "160", "62.54 (11.71)", "316 (65.3)", "421 (88.1)", "55 (11.5)", "2 (0.4)", "0 (0.0)"], ["LIHC", "377", "50", "60.15 (13.79)", "285 (66.7)", "221 (53.4)", "24 (5.8)", "167 (40.3)", "2 (0.5)"], ["LUAD", "473", "32", "65.37 (10.29)", "236 (46.7)", "392 (86.2)", "57 (12.5)", "6 (1.3)", "0 (0.0)"], ["LUSC", "370", "42", "68.23 (8.85)", "303 (73.5)", "308 (90.3)", "25 (7.3)", "8 (2.3)", "0 (0.0)"], ["PAAD", "184", "10", "65.46 (11.10)", "108 (55.7)", "170 (89.5)", "8 (4.2)", "12 (6.3)", "0 (0.0)"], ["PCPG", "148", "8", "50.94 (3.12)", "66 (44.0)", "126 (86.3)", "14 (9.6)", "5 (3.4)", "1 (0.7)"], ["PRAD", "502", "50", "61.64 (6.77)", "552(100.0)", "195 (94.2)", "10 (4.8)", "2 (1.0)", "0 (0.0)"], ["READ", "98", "7", "63.57 (12.30)", "56 (53.8)", "76 (92.7)", "5 (6.1)", "1 (1.2)", "0 (0.0)"], ["SARC", "261", "4", "61.52 (14.62)", "120 (45.3)", "232 (90.6)", "18 (7.0)", "6 (2.3)", "0 (0.0)"], ["STAD", "395", "63", "65.78 (10.68)", "259 (65.2)", "255 (71.2)", "13 (3.6)", "89 (24.9)", "1 (0.3)"], ["THCA", "507", "56", "47.64 (15.94)", "150 (26.6)", "372 (80.7)", "33 (7.2)", "55 (11.9)", "1 (0.2)"], ["UCEC", "438", "46", "64.54 (11.19)", "0 (0.0)", "318 (72.1)", "105 (23.8)", "9 (2.0)", "9 (2.0)"], ["Total", "6795", "922", "61.85 (13.60)", "3730 (48.9)", "5330 (80.4)", "737 (11.1)", "536 (8.1)", "28 (0.4)"]], "row_count": 22, "column_count": 9, "numeric_cells": 168, "header_rows": 1, "locator": "section[8]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:31324166:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:46049c67a95b14d230be79a9d89ae495f7d55ba05ceac328ecc12ad80fecbe5e", "bytes": 1390, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[2]#Tab2", "version": null, "note": "P-values based on comparisons of the predicted FCO (%) between tumor and nontumor normal samples across different TCGA studies. 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