title: Single-chromosome Gains Commonly Function as Tumor Suppressors.
abstract: Aneuploidy is a hallmark of cancer, although its effects on tumorigenesis are unclear. Here, we investigated the relationship between aneuploidy and cancer development using cells engineered to harbor single extra chromosomes. We found that nearly all trisomic cell lines grew poorly in vitro and as xenografts, relative to genetically matched euploid cells. Moreover, the activation of several oncogenic pathways failed to alleviate the fitness defect induced by aneuploidy. However, following prolonged growth, trisomic cells acquired additional chromosomal alterations that were largely absent from their euploid counterparts and that correlated with improved fitness. Thus, while single-chromosome gains can suppress transformation, the genome-destabilizing effects of aneuploidy confer an evolutionary flexibility that may contribute to the aggressive growth of advanced malignancies with complex karyotypes.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: sheltzer@cshl.edu.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Sheltzer
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Julie H
authors.initials: JH
authors.lastname: Ko
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Replogle
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Habibe Burgos
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Erica S
authors.initials: ES
authors.lastname: Chung
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Meehl
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Sayles
authors.affiliation: Group Maintenance of Genome Stability, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Passerini
authors.affiliation: Group Maintenance of Genome Stability, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany; Department of Molecular Genetics, University of Kaiserslautern, 67663 Kaiserslautern, Germany.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Storchova
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: angelika@mit.edu.
authors.forename: Angelika
authors.initials: A
authors.lastname: Amon
mesh_terms: D000782:Aneuploidy; D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D011905:Genes, ras; D042822:Genomic Instability; D045325:HCT116 Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000517:prevention & control; D009857:Oncogenes
keywords: aneuploidy; chromosomal instability; genome dosage imbalance; genomic instability; transformation