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  Unique features of the transcriptional response to model aneuploidy in human cells

Dürrbaum, M., Kuznetsova, A. Y., Passerini, V., Stingele, S., Stoehr, G., & Storchova, Z. (2014). Unique features of the transcriptional response to model aneuploidy in human cells. BMC GENOMICS, 15: 139. doi:10.1186/1471-2164-15-139.

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 Creators:
Dürrbaum, Milena1, Author              
Kuznetsova, Anastasia Yurievna1, Author              
Passerini, Verena1, Author              
Stingele, Silvia1, Author              
Stoehr, Gabriele2, Author              
Storchova, Zuzana1, Author              
Affiliations:
1Storchova, Zuzana / Maintenance of Genome Stability, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565171              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: CANCER CHROMOSOMAL INSTABILITY; YEAST-CELLS; CONSEQUENCES; STRESS; IDENTIFICATION; TUMORIGENESIS; PROTEOMICS; KARYOTYPE; PROTEINS; ARREST
 Abstract: Background: Aneuploidy, a karyotype deviating from multiples of a haploid chromosome set, affects the physiology of eukaryotes. In humans, aneuploidy is linked to pathological defects such as developmental abnormalities, mental retardation or cancer, but the underlying mechanisms remain elusive. There are many different types and origins of aneuploidy, but whether there is a uniform cellular response to aneuploidy in human cells has not been addressed so far. Results: Here we evaluate the transcription profiles of eleven trisomic and tetrasomic cell lines and two cell lines with complex aneuploid karyotypes. We identify a characteristic aneuploidy response pattern defined by upregulation of genes linked to endoplasmic reticulum, Golgi apparatus and lysosomes, and downregulation of DNA replication, transcription as well as ribosomes. Strikingly, complex aneuploidy elicits the same transcriptional changes as trisomy. To uncover the triggers of the response, we compared the profiles with transcription changes in human cells subjected to stress conditions. Interestingly, we found an overlap only with the response to treatment with the autophagy inhibitor bafilomycin A1. Finally, we identified 23 genes whose expression is significantly altered in all aneuploids and which may thus serve as aneuploidy markers. Conclusions: Our analysis shows that despite the variability in chromosome content, aneuploidy triggers uniform transcriptional response in human cells. A common response independent of the type of aneuploidy might be exploited as a novel target for cancer therapy. Moreover, the potential aneuploidy markers identified in our analysis might represent novel biomarkers to assess the malignant potential of a tumor.

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Language(s): eng - English
 Dates: 2014
 Publication Status: Published online
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000332601300003
DOI: 10.1186/1471-2164-15-139
 Degree: -

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Title: BMC GENOMICS
Source Genre: Journal
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Publ. Info: 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND : BIOMED CENTRAL LTD
Pages: - Volume / Issue: 15 Sequence Number: 139 Start / End Page: - Identifier: ISSN: 1471-2164