Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC.
Cancer/testis antigens (CTAs) were first discovered as immunogenic targets normally expressed in germline cells, but differentially expressed in a variety of human cancers. In this study, we used an integrative epigenetic screening approach to identify coordinately expressed genes in human non-small...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-12-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2781168?pdf=render |
| _version_ | 1818859244399624192 |
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| author | Chad A Glazer Ian M Smith Michael F Ochs Shahnaz Begum William Westra Steven S Chang Wenyue Sun Sheetal Bhan Zubair Khan Steven Ahrendt Joseph A Califano |
| author_facet | Chad A Glazer Ian M Smith Michael F Ochs Shahnaz Begum William Westra Steven S Chang Wenyue Sun Sheetal Bhan Zubair Khan Steven Ahrendt Joseph A Califano |
| author_sort | Chad A Glazer |
| collection | DOAJ |
| description | Cancer/testis antigens (CTAs) were first discovered as immunogenic targets normally expressed in germline cells, but differentially expressed in a variety of human cancers. In this study, we used an integrative epigenetic screening approach to identify coordinately expressed genes in human non-small cell lung cancer (NSCLC) whose transcription is driven by promoter demethylation.Our screening approach found 290 significant genes from the over 47,000 transcripts incorporated in the Affymetrix Human Genome U133 Plus 2.0 expression array. Of the top 55 candidates, 10 showed both differential overexpression and promoter region hypomethylation in NSCLC. Surprisingly, 6 of the 10 genes discovered by this approach were CTAs. Using a separate cohort of primary tumor and normal tissue, we validated NSCLC promoter hypomethylation and increased expression by quantitative RT-PCR for all 10 genes. We noted significant, coordinated coexpression of multiple target genes, as well as coordinated promoter demethylation, in a large set of individual tumors that was associated with the SCC subtype of NSCLC. In addition, we identified 2 novel target genes that exhibited growth-promoting effects in multiple cell lines.Coordinated promoter demethylation in NSCLC is associated with aberrant expression of CTAs and potential, novel candidate protooncogenes that can be identified using integrative discovery techniques. These findings have significant implications for discovery of novel CTAs and CT antigen directed immunotherapy. |
| first_indexed | 2024-12-19T09:09:06Z |
| format | Article |
| id | doaj.art-7c6eeb5410584081926577979bb1d986 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T09:09:06Z |
| publishDate | 2009-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7c6eeb5410584081926577979bb1d9862022-12-21T20:28:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-12-01412e818910.1371/journal.pone.0008189Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC.Chad A GlazerIan M SmithMichael F OchsShahnaz BegumWilliam WestraSteven S ChangWenyue SunSheetal BhanZubair KhanSteven AhrendtJoseph A CalifanoCancer/testis antigens (CTAs) were first discovered as immunogenic targets normally expressed in germline cells, but differentially expressed in a variety of human cancers. In this study, we used an integrative epigenetic screening approach to identify coordinately expressed genes in human non-small cell lung cancer (NSCLC) whose transcription is driven by promoter demethylation.Our screening approach found 290 significant genes from the over 47,000 transcripts incorporated in the Affymetrix Human Genome U133 Plus 2.0 expression array. Of the top 55 candidates, 10 showed both differential overexpression and promoter region hypomethylation in NSCLC. Surprisingly, 6 of the 10 genes discovered by this approach were CTAs. Using a separate cohort of primary tumor and normal tissue, we validated NSCLC promoter hypomethylation and increased expression by quantitative RT-PCR for all 10 genes. We noted significant, coordinated coexpression of multiple target genes, as well as coordinated promoter demethylation, in a large set of individual tumors that was associated with the SCC subtype of NSCLC. In addition, we identified 2 novel target genes that exhibited growth-promoting effects in multiple cell lines.Coordinated promoter demethylation in NSCLC is associated with aberrant expression of CTAs and potential, novel candidate protooncogenes that can be identified using integrative discovery techniques. These findings have significant implications for discovery of novel CTAs and CT antigen directed immunotherapy.http://europepmc.org/articles/PMC2781168?pdf=render |
| spellingShingle | Chad A Glazer Ian M Smith Michael F Ochs Shahnaz Begum William Westra Steven S Chang Wenyue Sun Sheetal Bhan Zubair Khan Steven Ahrendt Joseph A Califano Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC. PLoS ONE |
| title | Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC. |
| title_full | Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC. |
| title_fullStr | Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC. |
| title_full_unstemmed | Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC. |
| title_short | Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC. |
| title_sort | integrative discovery of epigenetically derepressed cancer testis antigens in nsclc |
| url | http://europepmc.org/articles/PMC2781168?pdf=render |
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