Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA116193 | ENA |
REPOSITORIES: ENA
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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: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.
2009-07-28 | GSE16559 | GEO
Project description:41 lung adenocarcinoma from never-smokers hybridized on Illumina SNP arrays on 13 HumanCNV370-Quadv3 chips. High-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in 41 never smokers for identification of new minimal common regions (MCR) of gain or loss. The SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity.The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers. A 'Cartes d'Identite des Tumeurs' (CIT) project from the French National League Against Cancer (http://cit.ligue-cancer.net) 41 samples hybridized on Illumina SNP arrays. Submitter : Fabien PETEL petelf@ligue-cancer.net . Project leader : Pr Pierre FOURET pierre.fouret@psl.aphp.fr
2011-07-28 | E-TABM-1169 | biostudies-arrayexpress
Project description:Mesothelioma integrative genomics: DNA methylation
| PRJNA129639 | ENA
Project description:Human lung adenocarcinoma DNA methylation profiling by MSNP
| PRJNA155827 | ENA
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
2011-08-25 | GSE23936 | GEO
Project description:DNA methylation analysis of lung adenocarcinoma and adjacent non-tumor tissues
| PRJNA339546 | ENA
Project description:We screened pleural effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass spectrometry-(MS-) based proteomics using isobaric tags for relative and absolute quantification (iTRAQ) and used narrow range immobilized pH gradient/high resolution isoelectric focusing (IPG/HiRIEF; pH 4 to 4.25) prior to analysis by nano liquid chromatography-coupled MS/MS. Pleural effusions from patients with malignant mesothelioma (n=6), lung adenocarcinoma (n=6), or benign mesotheliosis (n=7) were analyzed, and more than 1,300 proteins were identified.
2014-01-14 | PXD000531 | Pride
Project description:Multi-platform Characterization of Stage I Lung Adenocarcinoma (Genome-wide DNA Methylation)
| PRJNA267607 | ENA