Combined DNA methylation and gene expression profiling in gastrointestinal stromal tumors reveals hypomethylation of SPP1 as an independent prognostic factor
Haller F, Zhang JD, Moskalev E, Braun A, Otto C, Geddert H, Riazalhosseini Y, Ward A, Balwierz A, Schaefer IM, Cameron S, Ghadimi BM, Agaimy A, Fletcher JA, Hoheisel J, Hartmann A, Werner M, Wiemann S, Sahin O (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 136
Pages Range: 1013-23
Journal Issue: 5
DOI: 10.1002/ijc.29088
Abstract
Gastrointestinal stromal tumors (GISTs) have distinct gene expression patterns according to localization, genotype and aggressiveness. DNA methylation at CpG dinucleotides is an important mechanism for regulation of gene expression. We performed targeted DNA methylation analysis of 1.505 CpG loci in 807 cancer-related genes in a cohort of 76 GISTs, combined with genome-wide mRNA expression analysis in 22 GISTs, to identify signatures associated with clinicopathological parameters and prognosis. Principal component analysis revealed distinct DNA methylation patterns associated with anatomical localization, genotype, mitotic counts and clinical follow-up. Methylation of a single CpG dinucleotide in the non-CpG island promoter of SPP1 was significantly correlated with shorter disease-free survival. Hypomethylation of this CpG was an independent prognostic parameter in a multivariate analysis compared to anatomical localization, genotype, tumor size and mitotic counts in a cohort of 141 GISTs with clinical follow-up. The epigenetic regulation of SPP1 was confirmed in vitro, and the functional impact of SPP1 protein on tumorigenesis-related signaling pathways was demonstrated. In summary, SPP1 promoter methylation is a novel and independent prognostic parameter in GISTs, and might be helpful in estimating the aggressiveness of GISTs from the intermediate-risk category.
Authors with CRIS profile
Evgeny Moskalev
Institute of Pathology
Abbas Agaimy
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie
Arndt Hartmann
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie
Involved external institutions
Deutsches Krebsforschungszentrum (DKFZ)
Germany (DE)
Albert-Ludwigs-Universität Freiburg
Germany (DE)
St. Vincentius-Kliniken / ViDia Kliniken
Germany (DE)
Georg-August-Universität Göttingen
Germany (DE)
Brigham and Women's Hospital (BWH)
United States (USA) (US)
Germany (DE)
Albert-Ludwigs-Universität Freiburg
Germany (DE)
St. Vincentius-Kliniken / ViDia Kliniken
Germany (DE)
Georg-August-Universität Göttingen
Germany (DE)
Brigham and Women's Hospital (BWH)
United States (USA) (US)
How to cite
APA:
Haller, F., Zhang, J.D., Moskalev, E., Braun, A., Otto, C., Geddert, H.,... Sahin, O. (2015). Combined DNA methylation and gene expression profiling in gastrointestinal stromal tumors reveals hypomethylation of SPP1 as an independent prognostic factor. International Journal of Cancer, 136(5), 1013-23. https://doi.org/10.1002/ijc.29088
MLA:
Haller, Florian, et al. "Combined DNA methylation and gene expression profiling in gastrointestinal stromal tumors reveals hypomethylation of SPP1 as an independent prognostic factor." International Journal of Cancer 136.5 (2015): 1013-23.
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