Abstract:
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.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Bjaanæs MM,Fleischer T,Halvorsen AR,Daunay A,Busato F,Solberg S,Jørgensen L,Kure E,Edvardsen H,Børresen-Dale AL,Brustugun OT,Tost J,Kristensen V,Helland Ådoi
10.1016/j.molonc.2015.10.021subject
Has Abstractpub_date
2016-02-01 00:00:00pages
330-43issue
2eissn
1574-7891issn
1878-0261pii
S1574-7891(15)00199-4journal_volume
10pub_type
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