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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 03, 2007 |
| Title |
A Genome-wide Screen for Hypermethylated Genes in Lung Cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Abstract
Background: Promoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The “rules” governing which genes are methylated during the pathogenesis of individual cancers, how specific methylation profiles are initially established, or what determines tumor-type specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype identify pathways important as therapeutic targets.
Methods and Findings: In an effort to identify new cancer-specific methylation markers, we employed a high throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5’ CpG islands, are induced from undetectable levels by 5-aza-2’-deoxycytidine (5-aza) in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (N=20) and adjacent non-malignant tissue showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or lymphocytes. We studied the eight most frequently and specifically methylated genes from our lung cancer data set in breast cancer (N=37), colon cancer (N=24), and prostate cancer (N=24) along with counterpart non-malignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors.
Conclusions: By using a systematic biological screen we identified multiple genes that are methylated with high penetrance in primary lung, breast, colon, and prostate cancers. The cross-tumor methylation pattern we observed for these novel markers suggests that we have identified a partial promoter hypermethylation signature for these common malignancies. These data suggest that while tumors in different tissues vary substantially with respect to gene expression, there may be commonalities in their promoter methylation profiles that represent potential targets for early detection screening or therapeutic intervention.
Keywords: Cell line comparison
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| Overall design |
Drug treatment: control, 100 nM, 1 uM
Cancer vs. Normal Comparison: NSCLC vs. Normal
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| Contributor(s) |
Shames DS, Girard L, Gao B, Sato M, Lewis CM, Shivapurkar N, Jiang A, Perou CM, Kim YH, Pollack JR, Fong KM, Lam CD, Wong M, Shyr Y, Nanda R, Olopade OL, Gerald W, Euhus DM, Shay JW, Gazdar AF, Minna JD |
| Citation(s) |
17194187 |
| |
| Submission date |
Sep 12, 2006 |
| Last update date |
Mar 25, 2019 |
| Contact name |
David S Shames |
| E-mail(s) |
[email protected]
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| Phone |
650-225-7559
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| Organization name |
Genentech Inc
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| Department |
Oncology Biomarker Development
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| Lab |
Shames
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| Street address |
1 DNA Way
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| City |
South San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94080 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (42)
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| GSM134904 |
H1993 Control treatment group (DMSO) |
| GSM134906 |
H1993 Low dose 5-aza treatment group (100 nM) |
| GSM134908 |
H1993 High dose 5-aza treatment group (1000 nM) |
| GSM134909 |
H1299 Control group treatment |
| GSM134910 |
H1299 Low dose 5-aza treatment group (100 nM) |
| GSM134911 |
H460 Low dose treatment group (100 nM) |
| GSM134912 |
A549 Low dose treatment group (100 nM). |
| GSM134914 |
HBEC2 Low dose treatment group (100 nM). |
| GSM134916 |
HBEC3 Low dose treatment group (100 nM). |
| GSM134918 |
HBEC4 Low dose treatment group (100 nM). |
| GSM134920 |
HBEC4 Control treatment group (DMSO). |
| GSM134924 |
HBEC2 Control treatment group (DMSO) |
| GSM134927 |
H460 Control treatment group (DMSO) |
| GSM134931 |
HBEC2-Rep2 Control treatment group (DMSO). |
| GSM134933 |
HBEC3-Rep2 Control treatment group (DMSO) |
| GSM134936 |
HBEC4-Rep2 Control treatment group (DMSO) |
| GSM134938 |
A549 Control treatment group (DMSO). |
| GSM134942 |
HBEC4 High dose treatment group (1000 nM) |
| GSM134944 |
H1299 High dose treatment group (1000 nM). |
| GSM134945 |
A549 High dose treatment group (1000 nM). |
| GSM134946 |
H460 High dose treatment group (1000 nM). |
| GSM134947 |
HBEC2 High dose treatment group (1000 nM). |
| GSM134948 |
HBEC3 High dose treatment group (1000 nM). |
| GSM134949 |
HBEC4-Rep2 High dose treatment group (1000 nM). |
| GSM134950 |
HBEC2-Rep2 High dose treatment group (1000 nM). |
| GSM134951 |
HBEC3-Rep2 High dose treatment group (1000 nM). |
| GSM154492 |
H157 Control group treatment. |
| GSM154493 |
H157 Low dose treatment group (100 nM) |
| GSM154494 |
H157 High dose treatment group |
| GSM154495 |
H1819 Control group treatment |
| GSM154496 |
H1819 Lose dose treatment group (100 nM) |
| GSM154497 |
H1819 High dose treatment group (1000 nM) |
| GSM154498 |
HBEC2 Control group treatment |
| GSM155191 |
H526 Control treatment group |
| GSM155193 |
H526 High dose treatment group (1000 nM) |
| GSM155194 |
MCF7 Control treatment group |
| GSM155196 |
MCF7 High dose treatment group |
| GSM155197 |
HCT116 Control treatment group |
| GSM155198 |
HCT116 High dose treatment group |
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| Relations |
| BioProject |
PRJNA97201 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE5816_RAW.tar |
347.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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