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@ARTICLE{Haller:126653,
author = {F. Haller and J. D. Zhang$^*$ and E. A. Moskalev and A.
Braun and C. Otto and H. Geddert and Y. Riazalhosseini$^*$
and A. Ward$^*$ and A. Balwierz$^*$ and I.-M. Schaefer and
S. Cameron and B. M. Ghadimi and A. Agaimy and J. A.
Fletcher and J. Hoheisel$^*$ and A. Hartmann and M. Werner
and S. Wiemann$^*$ and O. Sahin$^*$},
title = {{C}ombined {DNA} methylation and gene expression profiling
in gastrointestinal stromal tumors reveals hypomethylation
of {SPP}1 as an independent prognostic factor.},
journal = {International journal of cancer},
volume = {136},
number = {5},
issn = {0020-7136},
address = {Bognor Regis},
publisher = {Wiley-Liss},
reportid = {DKFZ-2017-02681},
pages = {1013 - 1023},
year = {2015},
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.},
keywords = {Biomarkers, Tumor (NLM Chemicals) / SPP1 protein, human
(NLM Chemicals) / Osteopontin (NLM Chemicals)},
cin = {B050 / B070 / W110},
ddc = {610},
cid = {I:(DE-He78)B050-20160331 / I:(DE-He78)B070-20160331 /
I:(DE-He78)W110-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25046773},
doi = {10.1002/ijc.29088},
url = {https://inrepo02.dkfz.de/record/126653},
}