Cancer-associated gene expression imbalances are conventionally studied at the genomic, epigenomic and transcriptomic levels. Given the relevance of translational control in determining cell phenotypes, we evaluated the translatome, i.e., the transcriptome engaged in translation, as a descriptor of the effects of genetic instability in cancer. We performed this evaluation in high-risk neuroblastomas, which are characterized by a low frequency of point mutations or known cancer-driving genes and by the presence of several segmental chromosomal aberrations that produce gene-copy imbalances that guide aggressiveness. We thus integrated genome, transcriptome, translatome and miRome profiles in a representative panel of high-risk neuroblastoma cell lines. We identified a number of genes whose genomic imbalance was corrected by compensatory adaptations in translational efficiency. The transcriptomic level of these genes was predictive of poor prognosis in more than half of cases and the genomic imbalances found in their loci were shared by 27 other tumor types. This homeostatic process is also not limited to copy number-altered genes, as we showed the translational stoichiometric rebalance of histone genes. We suggest that the translational buffering of fluctuations in these dose-sensitive transcripts is a potential driving process of neuroblastoma evolution.

Translational compensation of genomic instability in neuroblastoma / Dassi, Erik; Greco, Valentina; Sidarovich, Viktoryia; Zuccotti, Paola; Arseni, Natalia; Scaruffi, Paola; Tonini, Gianpaolo; Quattrone, Alessandro. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 5:(2015), pp. 1436401-1436413. [10.1038/srep14364]

Translational compensation of genomic instability in neuroblastoma

Dassi, Erik;Greco, Valentina;Sidarovich, Viktoryia;Zuccotti, Paola;Quattrone, Alessandro
2015-01-01

Abstract

Cancer-associated gene expression imbalances are conventionally studied at the genomic, epigenomic and transcriptomic levels. Given the relevance of translational control in determining cell phenotypes, we evaluated the translatome, i.e., the transcriptome engaged in translation, as a descriptor of the effects of genetic instability in cancer. We performed this evaluation in high-risk neuroblastomas, which are characterized by a low frequency of point mutations or known cancer-driving genes and by the presence of several segmental chromosomal aberrations that produce gene-copy imbalances that guide aggressiveness. We thus integrated genome, transcriptome, translatome and miRome profiles in a representative panel of high-risk neuroblastoma cell lines. We identified a number of genes whose genomic imbalance was corrected by compensatory adaptations in translational efficiency. The transcriptomic level of these genes was predictive of poor prognosis in more than half of cases and the genomic imbalances found in their loci were shared by 27 other tumor types. This homeostatic process is also not limited to copy number-altered genes, as we showed the translational stoichiometric rebalance of histone genes. We suggest that the translational buffering of fluctuations in these dose-sensitive transcripts is a potential driving process of neuroblastoma evolution.
2015
Dassi, Erik; Greco, Valentina; Sidarovich, Viktoryia; Zuccotti, Paola; Arseni, Natalia; Scaruffi, Paola; Tonini, Gianpaolo; Quattrone, Alessandro...espandi
Translational compensation of genomic instability in neuroblastoma / Dassi, Erik; Greco, Valentina; Sidarovich, Viktoryia; Zuccotti, Paola; Arseni, Natalia; Scaruffi, Paola; Tonini, Gianpaolo; Quattrone, Alessandro. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 5:(2015), pp. 1436401-1436413. [10.1038/srep14364]
File in questo prodotto:
File Dimensione Formato  
2015-SciRep-Dassi-srep14364.pdf

accesso aperto

Tipologia: Versione editoriale (Publisher’s layout)
Licenza: Creative commons
Dimensione 2.02 MB
Formato Adobe PDF
2.02 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/179138
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 8
social impact