近日，美国哈佛大学Bradley E. Bernstein、Martin J. Aryee等研究人员合作发现，大规模拓扑变化抑制结直肠癌恶性进展。这一研究成果于2020年8月24日在线发表在国际学术期刊《细胞》上。

Title: Large-Scale Topological Changes Restrain Malignant Progression in Colorectal Cancer

Author: Sarah E. Johnstone, Alejandro Reyes, Yifeng Qi, Carmen Adriaens, Esmat Hegazi, Karin Pelka, Jonathan H. Chen, Luli S. Zou, Yotam Drier, Vivian Hecht, Noam Shoresh, Martin K. Selig, Caleb A. Lareau, Sowmya Iyer, Son C. Nguyen, Eric F. Joyce, Nir Hacohen, Rafael A. Irizarry, Bin Zhang, Martin J. Aryee, Bradley E. Bernstein

Issue&Volume: 2020-08-24

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 integratedtopological maps for colon tumors and normal colons with epigenetic, transcriptional,and imaging data to characterize alterations to chromatin loops, topologically associateddomains, and large-scale compartments. We found that spatial partitioning of the openand closed genome compartments is profoundly compromised in tumors. This reorganizationis accompanied by compartment-specific hypomethylation and chromatin changes. Additionally,we identify a compartment at the interface between the canonical A and B compartmentsthat is reorganized in tumors. Remarkably, similar shifts were evident in non-malignantcells that have accumulated excess divisions. Our analyses suggest that these topologicalchanges repress stemness and invasion programs while inducing anti-tumor immunitygenes and may therefore restrain malignant progression. Our findings call into questionthe conventional view that tumor-associated epigenomic alterations are primarily oncogenic.

DOI: 10.1016/j.cell.2020.07.030

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30938-7