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Status |
Public on Oct 05, 2014 |
Title |
Genome-wide DNA methylation analysis of lung carcinoma |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by genome tiling array
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Summary |
Lung cancer is the worldwide leading cause of death from cancer. DNA methylation in gene promoter regions is a major mechanism of gene expression regulation that may promote tumorigenesis. However, whether clinically relevant subgroups based on DNA methylation patterns exist in lung cancer is not well studied.
We performed whole-genome methylation analysis using 450K Illumina BeadArrays on 124 tumors including 83 adenocarcinomas, 23 squamous cell carcinomas, one adenosquamous cancer, five large cell carcinomas, nine large cell neuroendocrine carcinomas (LCNEC), three small cell carcinomas (SCLC) and 12 normal lung tissues. Unsupervised class discovery was performed to identify DNA methylation subgroups with clinicopathological and molecular features. Subgroups were validated in two independent NSCLC cohorts.
Unsupervised analysis identified five DNA methylation subgroups (epitypes). One epitype was distinctly associated with neuroendocrine tumors (LCNEC and SCLC). For adenocarcinoma, in both discovery and validation cohorts, remaining four epitypes were associated with differences in clinicopathological and molecular features, including global hypomethylation, promoter hypermethylation, copy number alterations, expression of proliferation-associated genes, association with unsupervised and supervised gene expression phenotypes, KRAS, TP53, KEAP1, SMARCA4, and STK11 mutations, smoking history, and patient outcome.
Based on a multicohort approach we conducted a comprehensive survey of genome-wide DNA methylation in lung cancer, identifying a distinct neuroendocrine epitype and four adenocarcinoma epitypes associated with molecular and clinicopathological characteristics, and patient outcome. Our results bring further understanding of the epigenetic characteristics and molecular diversity in lung cancer generally and in adenocarcinoma specifically.
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Overall design |
Genome-wide DNA methylation analysis of 124 lung carcinomas and 12 normal lung tissues using Illumina Human Methylation 450K v1.0 Beadchips.
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Contributor(s) |
Karlsson A, Jönsson M, Lauss M, Brunnström H, Jönsson P, Jönsson G, Ringner M, Planck M, Staaf J |
Citation(s) |
25278450 |
Submission date |
Mar 19, 2014 |
Last update date |
Mar 22, 2019 |
Contact name |
Johan Staaf |
Organization name |
SCIBLU - Swegene Centre for Integrative Biology at Lund University
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Street address |
Medicon Village
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City |
Lund |
ZIP/Postal code |
SE-223 81 |
Country |
Sweden |
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Platforms (1) |
GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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Samples (136)
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This SubSeries is part of SuperSeries: |
GSE60645 |
Genome-wide DNA methylation and expression analysis of lung carcinoma |
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Relations |
BioProject |
PRJNA242349 |
Supplementary file |
Size |
Download |
File type/resource |
GSE56044_GEO_Annotations.xls.gz |
20.1 Kb |
(ftp)(http) |
XLS |
GSE56044_RAW.tar |
183.1 Mb |
(http)(custom) |
TAR |
GSE56044_methylation_raw.txt.gz |
832.9 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
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