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dc.contributor.authorLind, Guro E
dc.contributor.authorThorstensen, Lin
dc.contributor.authorLøvig, Tone
dc.contributor.authorMeling, Gunn I
dc.contributor.authorHamelin, Richard
dc.contributor.authorRognum, Torleiv O
dc.contributor.authorEsteller, Manel
dc.contributor.authorLothe, Ragnhild A
dc.date.accessioned2015-10-09T01:01:45Z
dc.date.available2015-10-09T01:01:45Z
dc.date.issued2004
dc.identifier.citationMolecular Cancer. 2004 Oct 11;3(1):28
dc.identifier.urihttp://hdl.handle.net/10852/46253
dc.description.abstractBackground Tumor cell lines are commonly used as experimental tools in cancer research, but their relevance for the in vivo situation is debated. In a series of 11 microsatellite stable (MSS) and 9 microsatellite unstable (MSI) colon cancer cell lines and primary colon carcinomas (25 MSS and 28 MSI) with known ploidy stem line and APC, KRAS, and TP53 mutation status, we analyzed the promoter methylation of the following genes: hMLH1, MGMT, p16 INK4a(CDKN2A α-transcript), p14 ARF(CDKN2A β-transcript), APC, and E-cadherin (CDH1). We compared the DNA methylation profiles of the cell lines with those of the primary tumors. Finally, we examined if the epigenetic changes were associated with known genetic markers and/or clinicopathological variables. Results The cell lines and primary tumors generally showed similar overall distribution and frequencies of gene methylation. Among the cell lines, 15%, 50%, 75%, 65%, 20% and 15% showed promoter methylation for hMLH1, MGMT, p16 INK4a, p14 ARF, APC, and E-cadherin, respectively, whereas 21%, 40%, 32%, 38%, 32%, and 40% of the primary tumors were methylated for the same genes. hMLH1 and p14 ARFwere significantly more often methylated in MSI than in MSS primary tumors, whereas the remaining four genes showed similar methylation frequencies in the two groups. Methylation of p14 ARF, which indirectly inactivates TP53, was seen more frequently in tumors with normal TP53 than in mutated samples, but the difference was not statistically significant. Methylation of p14 ARFand p16 INK4awas often present in the same primary tumors, but association to diploidy, MSI, right-sided location and female gender was only significant for p14 ARF. E-cadherin was methylated in 14/34 tumors with altered APC further stimulating WNT signaling. Conclusions The present study shows that colon cancer cell lines are in general relevant in vitro models, comparable with the in vivo situation, as the cell lines display many of the same molecular alterations as do the primary carcinomas. The combined pattern of epigenetic and genetic aberrations in the primary carcinomas reveals associations between them as well as to clinicopathological variables, and may aid in the future molecular assisted classification of clinically distinct stages.
dc.language.isoeng
dc.rightsLind et al; licensee Biomed Central Ltd.
dc.rightsAttribution 2.0 Generic
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/
dc.titleA CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines
dc.typeJournal article
dc.date.updated2015-10-09T01:01:45Z
dc.creator.authorLind, Guro E
dc.creator.authorThorstensen, Lin
dc.creator.authorLøvig, Tone
dc.creator.authorMeling, Gunn I
dc.creator.authorHamelin, Richard
dc.creator.authorRognum, Torleiv O
dc.creator.authorEsteller, Manel
dc.creator.authorLothe, Ragnhild A
dc.identifier.doihttp://dx.doi.org/10.1186/1476-4598-3-28
dc.identifier.urnURN:NBN:no-50440
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/46253/1/12943_2004_Article_79.pdf
dc.type.versionPublishedVersion
cristin.articleid28


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