Large-Scale Topological Changes Restrain Malignant Progression in Colorectal Cancer.
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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MEDLINE
Assunto principal:
Cromatina
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Neoplasias Colorretais
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Regulação Neoplásica da Expressão Gênica
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Cromossomos
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Metilação de DNA
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Epigênese Genética
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article