Genome‐wide DNA methylation analyses in lung adenocarcinomas: Association with EGFR, KRAS and TP53 mutation status, gene expression and prognosis - CEA - Commissariat à l’énergie atomique et aux énergies alternatives Accéder directement au contenu
Article Dans Une Revue Molecular Oncology Année : 2015

Genome‐wide DNA methylation analyses in lung adenocarcinomas: Association with EGFR, KRAS and TP53 mutation status, gene expression and prognosis

Résumé

Background: DNA methylation alterations are early events in tumorigenesis and important in the regulation of gene expression in cancer cells. Lung cancer patients have in general a poor prognosis, and a deeper insight into the epigenetic landscape in lung adenocarcinoma tumors and its prognostic implications is needed. Results: We determined whole‐genome DNA methylation profiles of 164 fresh frozen lung adenocarcinoma samples and 19 samples of matched normal lung tissue using the Illumina Infinium 450K array. A large number of differentially methylated CpGs in lung adenocarcinoma tissue were identified, and specific methylation profiles were observed in tumors with mutations in the EGFR‐, KRAS‐ or TP53 genes and according to the patients' smoking status. The methylation levels were correlated with gene expression and both positive and negative correlations were seen. Methylation profiles of the tumor samples identified subtypes of tumors with distinct prognosis, including one subtype enriched for TP53 mutant tumors. A prognostic index based on the methylation levels of 33 CpGs was established, and was significantly associated with prognosis in the univariate analysis using an independent cohort of lung adenocarcinoma patients from The Cancer Genome Atlas project. CpGs in the HOX B and HOX C gene clusters were represented in the prognostic signature. Conclusions: Methylation differences mirror biologically important features in the etiology of lung adenocarcinomas and influence prognosis.
Fichier principal
Vignette du fichier
Molecular Oncology - 2015 - Bjaanæs - Genome‐wide DNA methylation analyses in lung adenocarcinomas Association with EGFR .pdf (2.11 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Licence : CC BY NC ND - Paternité - Pas d'utilisation commerciale - Pas de modification

Dates et versions

cea-04551201 , version 1 (18-04-2024)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Maria Moksnes Bjaanæs, Thomas Fleischer, Ann Rita Halvorsen, Antoine Daunay, Florence Busato, et al.. Genome‐wide DNA methylation analyses in lung adenocarcinomas: Association with EGFR, KRAS and TP53 mutation status, gene expression and prognosis. Molecular Oncology, 2015, 10 (2), pp.330-343. ⟨10.1016/j.molonc.2015.10.021⟩. ⟨cea-04551201⟩
0 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More