Genomics

Dataset Information

45

Near-tetraploid cells exhibit chromosome instability triggered by replication stress and enhanced invasive capabilities [aCGH]


ABSTRACT: A considerable proportion of tumors exhibit aneuploid karyotypes, likely resulting from the loss of chromosomes following whole genome duplication. Here, by using isogenic diploid and near-tetraploid clones derived from the same parental cell line, we aimed at exploring how polyploidization affects cellular functions and how tetraploidy generates chromosome instability. Gene expression profiling in near-tetraploid clones revealed a significant enrichment of genes involved in replication stress. This increased level of replication stress resulted in DNA damage, greater sensitivity to S-phase checkpoint inhibitors, and impaired proliferation caused by a cell cycle delay during S-phase. Additionally, replication stress promoted higher levels of intercellular heterogeneity and ongoing genomic instability, which we observed in the form of abnormal anaphases and prometaphase events. Finally, our data unveiled that near-tetraploid cells displayed increased migratory and invasive capacities, both in vitro and in primary colorectal tumors, thus providing physiological advantages to the cancer cell. Overall design: Single-cell clones were generated from the parental colorectal cell line DLD-1 to produce isogenic diploid and tetraploid clones.

INSTRUMENT(S): Agilent-022060 SurePrint G3 Human CGH Microarray 4x180K (Feature Number version, hg19/GRCh37)

SUBMITTER: Jordi Camps  

PROVIDER: GSE81303 | GEO | 2017-05-10

SECONDARY ACCESSION(S): PRJNA321437

REPOSITORIES: GEO

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