Human Gene Set: SATO_SILENCED_EPIGENETICALLY_IN_PANCREATIC_CANCER


Standard name SATO_SILENCED_EPIGENETICALLY_IN_PANCREATIC_CANCER
Systematic name M5542
Brief description 50 genes up-regulated in the pancreatic cancer cell lines (AsPC1, Hs766T, MiaPaCa2, Panc1) but not in the non-neoplastic cells (HPDE) by the combination of decitabine and TSA [PubChem=451668;5562].
Full description or abstract To identify potential targets for aberrant methylation in pancreatic cancer, we analyzed global changes in gene expression profiles of four pancreatic cancer cell lines after treatment with the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) and/or the histone deacetylase inhibitor trichostatin A. A substantial number of genes were induced 5-fold or greater by 5Aza-dC alone (631 transcripts), trichostatin A alone (1196 transcripts), and by treatment with both agents (857 transcripts). Four hundred and seventy-five genes were markedly (>5-fold) induced after 5Aza-dC treatment in pancreatic cancer cell lines but not in a nonneoplastic pancreatic epithelial cell line. The methylation status of 11 of these 475 genes was examined in a panel of 42 pancreatic cancers, and all 11 of these genes were aberrantly methylated in pancreatic cancer but rarely, if any, methylated in 10 normal pancreatic ductal epithelia. These genes include UCHL1 (methylated in 100% of 42 pancreatic cancers), NPTX2 (98%), SARP2 (95%), CLDN5 (93%), reprimo (86%), LHX1 (76%), WNT7A (71%), FOXE1 (69%), TJP2 (64%), CDH3 (19%), and ST14 (10%). Three of these 11 genes (NPTX2, SARP2, and CLDN5) were selected for further analysis in a larger panel of specimens, and aberrant methylation of at least one of these three genes was detectable in 100% of 43 primary pancreatic cancers and in 18 of 24 (75%) pancreatic juice samples obtained from patients with pancreatic cancer. Thus, a substantial number of genes are induced by 5Aza-dC treatment of pancreatic cancer cells, and many of them may represent novel targets for aberrant methylation in pancreatic carcinoma.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12839967   Authors: Sato N,Fukushima N,Maitra A,Matsubayashi H,Yeo CJ,Cameron JL,Hruban RH,Goggins M
Exact source http://pathology2.jhu.edu/pancreas/combi.pdf
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Source species Homo sapiens
Contributed by John Newman (University of Washington)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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Version history 3.0: Renamed from TSADAC_PANC50_UP

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