Non-small-cell lung tumor and normal lung tissue methylation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Brock Christensen
PROVIDER: E-GEOD-27902 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Key epigenetic changes associated with lung cancer development: results from dense methylation array profiling.
Nelson Heather H HH Marsit Carmen J CJ Christensen Brock C BC Houseman E Andres EA Kontic Milica M Wiemels Joseph L JL Karagas Margaret R MR Wrensch Margaret R MR Zheng Shichun S Wiencke John K JK Kelsey Karl T KT
Epigenetics 20120601 6
Epigenetic alterations are a common event in lung cancer and their identification can serve to inform on the carcinogenic process and provide clinically relevant biomarkers. Using paired tumor and non-tumor lung tissues from 146 individuals from three independent populations we sought to identify common changes in DNA methylation associated with the development of non-small cell lung cancer. Pathologically normal lung tissue taken at the time of cancer resection was matched to tumorous lung tiss ...[more]
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Project description:Pathologic differentiation of tissue of origin in tumors found in the lung can be challenging, with differentiation of mesothelioma and lung adenocarcinoma emblematic of this problem. Indeed, proper classification is essential for determination of treatment regimen for these diseases, making accurate and early diagnosis critical. Here we investigate the potential of epigenetic profiles of lung adenocarcinoma, mesothelioma, and non-malignant pulmonary tissues (n=285) as differentiation markers in an analysis of DNA methylation at 1413 autosomal CpG loci associated with 773 cancer-related genes. Using an unsupervised recursively-partitioned mixture modeling technique for all samples, the derived methylation profile classes were significantly associated with sample type (P < 0.0001). In a similar analysis restricted to tumors, methylation profile classes significantly predicted tumor type (P < 0.0001). Random forests classification of CpG methylation of tumors - which splits the data into training and test sets - accurately differentiated MPM from lung adenocarcinoma over 99% of the time (P < 0.0001). In a locus-by-locus comparison of CpG methylation between tumor types, 1266 CpG loci had significantly different methylation between tumors following correction for multiple comparisons (Q < 0.05); 61% had higher methylation in adenocarcinoma. Using the CpG loci with significant differential methylation in a pathways analysis revealed significant enrichment of methylated gene-loci in Cell Cycle Regulation, DNA Damage Response, PTEN Signaling, and Apoptosis Signaling pathways in lung adenocarcinoma when compared to mesothelioma. Methylation-profile-based differentiation of lung adenocarcinoma and mesothelioma is highly accurate, informs on the distinct etiologies of these diseases, and holds promise for clinical application. Mesotheliomas (n=158) and grossly non-tumorigenic parietal pleura (n=18) were obtained following surgical resection at Brigham and Womenâ??s Hospital through the International Mesothelioma Program from a pilot study conducted in 2002 (n=70) and an incident case series beginning in 2005 (n=88) with a participation rate of 85%. We used biopsy specimens from patients treated for NSCLC at the Massachusetts General Hospital from 1992 â?? 1996 (18) including lung adenocarcinomas (n=57) and non-malignant pulmonary tissues (n=48) (of which 22 (39%) were taken from the adenocarcinoma patients) (18). Additional normal lung tissues were obtained from the National Disease Research Interchange from donors free of lung malignancy (n=4).
2010-06-25 | E-GEOD-16559 | biostudies-arrayexpress
Project description:Solid tumors, including head and neck squamous cell carcinomas (HNSCC), arise as a result of genetic and epigenetic alterations in a sustained stress environment. Since it has been hypothesized that epigenetic alterations may act by providing the second carcinogenic hit in gene silencing, we sought to identify genome-wide DNA copy number alterations and CpG dinucleotide methylation events and examine the global/local relationships between these types of alterations in HNSCC. Importantly, we found that the global pattern of copy number alterations in these tumors was significantly associated with tumor methylation profiles. However at the local level, gene promoter regions did not exhibit a correlation between copy number and methylation , and the spectrum of genes affected by each type of alteration was unique. A case-series of 19 tumors and matched blood referents were hybrizided to Affymetrix Human Mapping 500k arrays and copy number was determined via HMM with Copy Number Analysis Tool v4.0.1. This study was designed to investigate the relationship between copy number and DNA methylation alterations in head and neck squamous cell carcinoma. Data in this submission relates to the methylation portion only. Each patient tumor has been de-identified and assigned a number (1-19). We included 11 normal head and neck samples, procured through the National Research Disease Interchange, that were used for reference when comparing tumor to normal. One ug of tissue DNA extracted using the Qiagen Blood and Tissue Kit was bisulfite-modified using a Zymo Research EZ DNA Methylation Kit. Samples were processed and arrayed on the Illumina GoldenGate Methylation Cancer Panel 1 at the University of California-San Francisco Institute for Genetics, Genomic Core Facility.
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2010-07-28 | E-GEOD-22290 | biostudies-arrayexpress
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2010-12-20 | E-GEOD-20395 | biostudies-arrayexpress
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