Human Gene Set: MARTINEZ_RESPONSE_TO_TRABECTEDIN_UP


Standard name MARTINEZ_RESPONSE_TO_TRABECTEDIN_UP
Systematic name M5190
Brief description Genes up-regulated in at least 8 of 11 sarcoma cell lines by trabectedin [PubChem=3199].
Full description or abstract Ecteinascidin 743 (ET-743; Yondelis, Trabectedin) is a marine anticancer agent that induces long-lasting objective remissions and tumor control in a subset of patients with pretreated/resistant soft-tissue sarcoma. Drug-induced tumor control is achievable in 22% of such patients, but there is no clear indication of the molecular features correlated with clinical sensitivity/resistance to ET-743. Nine low-passage, soft-tissue sarcoma cell lines, explanted from chemo-naive patients with different patterns of sensitivity, have been profiled with a cDNA microarray containing 6,700 cancer-related genes. The molecular signature of these cell lines was analyzed at baseline and at four different times after ET-743 exposure. The association of levels of TP53 mutation and TP73 expression with ET-743 sensitivity and cell cycle kinetics after treatment was also analyzed. Gene expression profile analysis revealed up-regulation of 86 genes and down-regulation of 244 genes in response to ET-743. The ET-743 gene expression signature identified a group of genes related with cell cycle control, stress, and DNA-damage response (JUNB, ATF3, CS-1, SAT, GADD45B, and ID2) that were up-regulated in all the cell lines studied. The transcriptional signature 72 hours after ET-743 administration, associated with ET-743 sensitivity, showed a more efficient induction of genes involved in DNA-damage response and apoptosis, such as RAD17, BRCA1, PAR4, CDKN1A, and P53DINP1, in the sensitive cell line group. The transcriptional signature described here may lead to the identification of ET-743 downstream mediators and transcription regulators and the proposal of strategies by which ET-743-sensitive tumors may be identified.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15897246   Authors: Martínez N,Sánchez-Beato M,Carnero A,Moneo V,Tercero JC,Fernández I,Navarrete M,Jimeno J,Piris MA
Exact source Suppl. data on the web
Related gene sets (show 1 additional gene sets from the source publication)

(show 6 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by John Newman (University of Washington)
Source platform or
identifier namespace		 HUMAN_GENE_SYMBOL
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 71 genes
Gene families ? Categorize these 71 genes by gene family
Show members (show 75 source identifiers mapped to 71 genes)
Version history 3.0: Renamed from ET743_SARCOMA_UP

See MSigDB license terms here. Please note that certain gene sets have special access terms.