Single-Chromosomal Gains Can Function as Metastasis Suppressors and Promoters in Colon Cancer

Vasudevan, A., Baruah, P.S., Smith, J.C., Wang, Z., Sayles, N. M., Andrews, P., Kendall, J., Leu, J., Chunduri, N.K., Levy, D., Wigler, M., Storchova, Z., Sheltzer, J. M. (February 2020) Single-Chromosomal Gains Can Function as Metastasis Suppressors and Promoters in Colon Cancer. Developmental Cell, 52 (4). pp. 413-428. ISSN 1534-5807

Abstract

High levels of cancer aneuploidy are frequently associated with poor prognosis. To examine the relationship between aneuploidy and cancer progression, we analyzed a series of congenic cell lines that harbor single extra chromosomes. We found that across 13 different trisomic cell lines, 12 trisomies suppressed invasiveness or were largely neutral, while a single trisomy increased metastatic behavior by triggering a partial epithelial-mesenchymal transition. In contrast, we discovered that chromosomal instability activates cGAS/STING signaling but strongly suppresses invasiveness. By analyzing patient copy-number data, we demonstrate that specific aneuploidies are associated with distinct outcomes, and the acquisition of certain aneuploidies is in fact linked with a favorable prognosis. Thus, aneuploidy is not a uniform driver of malignancy, and different aneuploidies can uniquely influence tumor progression. At the same time, the gain of a single chromosome is capable of inducing a profound cell state transition, thereby linking genomic plasticity, phenotypic plasticity, and metastasis.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics diseases & disorders > neoplasms bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomal duplications > aneuploidy organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell proliferation organs, tissues, organelles, cell types and functions > cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomal duplications bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > copy number variants organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent
CSHL Authors:	Sheltzer, Jason Wigler, Michael H. Levy, Dan Vasudevan, Anand Wang, Zihua Sayles, Nicole Andrews, Peter Kendall, Jude T. Baruah, Prasamit S. Smith, Joan C. Leu, Justin
Communities:	CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL labs > Levy lab CSHL labs > Sheltzer lab CSHL labs > Wigler lab
Depositing User:	Adrian Gomez
Date:	24 February 2020
Date Deposited:	06 Apr 2020 14:38
Last Modified:	01 Feb 2024 19:05
PMCID:	PMC7354079
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/39226

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