Gene Set: FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_UP

Standard name FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_UP
Systematic name M19957
Brief description Genes up-regulated in genomically unstable Ewing's sarcoma tumors compared to the stable ones.
Full description or abstract Ewing's sarcoma (ES) is characterized by specific chromosome translocations, the most common being t(11;22)(q24;q12). Additionally, other type of genetic abnormalities may occur and be relevant for explaining the variable tumour biology and clinical outcome. We have carried out a high-resolution array CGH and expression profiling on 25 ES tumour samples to characterize the DNA copy number aberrations (CNA) occurring in these tumours and determine their association with gene-expression profiles and clinical outcome. CNA were observed in 84% of the cases. We observed a median number of three aberrations per case. Besides numerical chromosome changes, smaller aberrations were found and defined at chromosomes 5p, 7q and 9p. All CNA were compiled to define the smallest overlapping regions of imbalance (SORI). A total of 35 SORI were delimited. Bioinformatics analyses were conducted to identify subgroups according to the pattern of genomic instability. Unsupervised and supervised clustering analysis (using SORI as variables) segregated the tumours in two distinct groups: one genomically stable (< or =3 CNA) and other genomically unstable (>3 CNA). The genomic unstable group showed a statistically significant shorter overall survival and was more refractory to chemotherapy. Expression profile analysis revealed significant differences between both groups. Genes related with chromosome segregation, DNA repair pathways and cell-cycle control were upregulated in the genomically unstable group. This report elucidates, for the first time, data about genomic instability in ES, based on CNA and expression profiling, and shows that a genomically unstable group of Ewing's tumours is correlated with a significant poor prognosis.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17952124   Authors: Ferreira BI,Alonso J,Carrillo J,Acquadro F,Largo C,Suela J,Teixeira MR,Cerveira N,Molares A,Goméz-López G,Pestaña A,Sastre A,Garcia-Miguel P,Cigudosa JC
Exact source Table 3S
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Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform HUMAN_SEQ_ACCESSION
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Version history 3.0: First introduced

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