Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide DNA methylation and expression analysis of lung carcinoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Johan Staaf

PROVIDER: E-GEOD-60645 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genome-wide DNA methylation analysis of lung carcinoma reveals one neuroendocrine and four adenocarcinoma epitypes associated with patient outcome.

Karlsson Anna A Jönsson Mats M Lauss Martin M Brunnström Hans H Jönsson Per P Borg Åke Å Jönsson Göran G Ringnér Markus M Planck Maria M Staaf Johan J

Clinical cancer research : an official journal of the American Association for Cancer Research 20141002 23

<h4>Purpose</h4>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 remains unclear.<h4>Experimental design</h4>Whole-genome DNA methylation analysis using 450K Illumina BeadArrays was performed on 12 normal lung tissues and 124 tumors, including 83 adenocarcin ...[more]

PMID: 25278450

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Project description: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. Genome-wide DNA methylation analysis of 124 lung carcinomas and 12 normal lung tissues using Illumina Human Methylation 450K v1.0 Beadchips.

Project description:Aberrant DNA methylation is frequently observed in breast cancer. However, the relationship between methylation patterns and the heterogeneity of breast cancer has not been comprehensively characterized. Whole-genome DNA methylation analysis using 450K Illumina BeadArrays was performed on 188 human breast tumors. Unsupervised bootstrap consensus clustering was performed to identify DNA methylation epigenetic subgroups (epitypes). The Cancer Genome Atlas data, incluing methylation profiles of 669 human breast tumors, was utilized for validation. The identified epitypes were characterized by integration with publicly available genome-wide data, including gene expression levels, DNA copy numbers, whole-exome sequencing data, and chromatin states. We identified seven breast cancer epitypes. One epitype was distinctly associated with basal-like tumors and with BRCA1 mutations, one epitype contained a subset of ERBB2-amplified tumors characterized by multiple additional amplifications and the most complex genomes, and one epitype displayed a methylation profile similar to normal epithelial cells. Luminal tumors were stratified into the remaining four epitypes, with differences in promoter hypermethylation, global hypomethylation, proliferative rates and genomic instability. We observed two dominant patterns of aberrant methylation in breast cancer. One pattern, constitutively methylated in both basal-like and luminal breast cancer, was linked to genes with promoters in a Polycomb-repressed state in normal epithelial cells and displayed no correlation to gene expression levels. The second pattern correlated with gene expression levels and was associated with methylation in luminal tumors and genes with active promoters in normal epithelial cells. Our results suggest that hypermethylation patterns in basal-like breast cancer may have limited influence on tumor progression and instead reflects the repressed chromatin state of the tissue of origin. On the contrary, hypermethylation patterns specific to luminal breast cancer influence gene expression, may contribute to tumor progression, and may present an actionable epigenetic alteration in some luminal breast cancers. Genome-wide DNA methylation analysis of 188 breast cancers using Illumina Human Methylation 450K Beadchips.

Dataset Information

Genome-wide DNA methylation and expression analysis of lung carcinoma

Publications

Genome-wide DNA methylation analysis of lung carcinoma reveals one neuroendocrine and four adenocarcinoma epitypes associated with patient outcome.

Similar Datasets

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