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dc.contributor.authorTabach, Yuvalen_US
dc.contributor.authorKogan-Sakin, Iraen_US
dc.contributor.authorBuganim, Yosefen_US
dc.contributor.authorSolomon, Hillaen_US
dc.contributor.authorGoldfinger, Naomien_US
dc.contributor.authorHovland, Randien_US
dc.contributor.authorKe, Xi-Songen_US
dc.contributor.authorØyan, Anne Margreteen_US
dc.contributor.authorKalland, Karl-Henningen_US
dc.contributor.authorRotter, Vardaen_US
dc.contributor.authorDomany, Eytanen_US
dc.date.accessioned2012-02-21T15:31:20Z
dc.date.available2012-02-21T15:31:20Z
dc.date.issued2011-01-31eng
dc.PublishedPLoS ONE 6(1): e14632en
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/1956/5636
dc.description.abstractDuplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a causal role in tumorigenesis. According to an alternative view, chromosomal imbalance is mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized by the over-expression of human telomerase catalytic subunit hTERT, and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that 20q amplification induced deregulation of several specific cancer-related pathways including the MAPK pathway, the p53 pathway and Polycomb group factors. In addition, activation of Myc, AML, B-Catenin and the ETS family transcription factors was identified as an important step in cancer development driven by 20q amplification. Finally we identified 13 "cancer initiating genes", located on 20q13, which were significantly over-expressed in many tumors, with expression levels correlated with tumor grade and outcome suggesting that these genes induce the malignant process upon 20q amplification.en_US
dc.language.isoengeng
dc.publisherPublic Library of Scienceeng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/eng
dc.titleAmplification of the 20q Chromosomal Arm Occurs Early in Tumorigenic Transformation and May Initiate Canceren_US
dc.typePeer reviewed
dc.typeJournal article
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2011 Tabach et al.
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0014632
dc.subject.nsiVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762eng


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