In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 9095-9095
Abstract:
9095 Background: Brain metastasis (MBM) represents one of the most significant causes of death in melanoma patients. Identification of clinically relevant markers is necessary to recognize patients with high risk of MBM development. Alterations in DNA methylation patterns have been recognized as a major epigenetic hallmark of metastasis initiation and progression. Methods: To generate a comprehensive genomic DNA methylation landscape of MBM, we performed genome-wide data integrative analyses examining the DNA methylation (Illumina HumanMethylation 450K), gene expression (Affymetrix HumanExon 1.0), and genotype (Affymetrix SNP 6.0) of specimens related to melanoma progression from normal to MBM (n=65). Results: We observed significant genome-wide hypomethylation and CpG island hypermethylation according to melanoma progression to the brain. To identify significant differentially methylated CpG sites between lymph node metastasis and MBM, we applied a strict statistical threshold (β-value difference 〉 0.3 and FDR-corrected p 〈 0.005). We identified the homeobox D (HOXD) gene family members amongst the most significantly affected genes. The influence on gene expression and the frequency of HOXD hypermethylation were verified using integrative analysis of publicly available data generated from 168 melanoma specimens. In a cohort of clinically annotated melanoma patients (n = 159), we demonstrated that hypermethylation of a genomic region in the HOXD gene cluster was significantly associated with shorter disease-free survival (p = 0.004) and overall survival (p = 0.002).Multivariate analysis confirmed the association with poorer survival (p = 0.01 and HR = 2.8; CI95%: 1.3-6.1). Conclusions: The use of genome-wide DNA methylation, gene expression, and genotyping integrative analyses allowed the identification of novel markers with functional and clinical implications for melanoma patients with brain metastasis.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.9095
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
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