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Large-Scale Topological Changes Restrain Malignant Progression in Colorectal Cancer.
Johnstone, Sarah E; Reyes, Alejandro; Qi, Yifeng; Adriaens, Carmen; Hegazi, Esmat; Pelka, Karin; Chen, Jonathan H; Zou, Luli S; Drier, Yotam; Hecht, Vivian; Shoresh, Noam; Selig, Martin K; Lareau, Caleb A; Iyer, Sowmya; Nguyen, Son C; Joyce, Eric F; Hacohen, Nir; Irizarry, Rafael A; Zhang, Bin; Aryee, Martin J; Bernstein, Bradley E.
Afiliação
  • Johnstone SE; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
  • Reyes A; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02215, USA.
  • Qi Y; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Adriaens C; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
  • Hegazi E; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
  • Pelka K; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
  • Chen JH; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
  • Zou LS; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02215, USA.
  • Drier Y; The Lautenberg Center for Immunology and Cancer Research, The Hebrew University, Jerusalem, Israel.
  • Hecht V; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
  • Shoresh N; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
  • Selig MK; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Lareau CA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02215, USA.
  • Iyer S; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Nguyen SC; Department of Genetics, Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Joyce EF; Department of Genetics, Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Hacohen N; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
  • Irizarry RA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02215, USA.
  • Zhang B; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Aryee MJ; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA; Department of Biostatistics, Harvard School of P
  • Bernstein BE; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA. Electronic address: bernstein.bradley@mgh.harvar
Cell ; 182(6): 1474-1489.e23, 2020 09 17.
Article em En | MEDLINE | ID: mdl-32841603
ABSTRACT
Widespread changes to DNA methylation and chromatin are well documented in cancer, but the fate of higher-order chromosomal structure remains obscure. Here we integrated topological maps for colon tumors and normal colons with epigenetic, transcriptional, and imaging data to characterize alterations to chromatin loops, topologically associated domains, and large-scale compartments. We found that spatial partitioning of the open and closed genome compartments is profoundly compromised in tumors. This reorganization is accompanied by compartment-specific hypomethylation and chromatin changes. Additionally, we identify a compartment at the interface between the canonical A and B compartments that is reorganized in tumors. Remarkably, similar shifts were evident in non-malignant cells that have accumulated excess divisions. Our analyses suggest that these topological changes repress stemness and invasion programs while inducing anti-tumor immunity genes and may therefore restrain malignant progression. Our findings call into question the conventional view that tumor-associated epigenomic alterations are primarily oncogenic.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Neoplasias Colorretais / Regulação Neoplásica da Expressão Gênica / Cromossomos / Metilação de DNA / Epigênese Genética Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Neoplasias Colorretais / Regulação Neoplásica da Expressão Gênica / Cromossomos / Metilação de DNA / Epigênese Genética Idioma: En Ano de publicação: 2020 Tipo de documento: Article