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@ARTICLE{Wrage:127812,
author = {M. Wrage and W. Hagmann$^*$ and D. Kemming and F. G.
Uzunoglu and S. Riethdorf and K. Effenberger and M. Westphal
and K. Lamszus and S.-Z. Kim and N. Becker$^*$ and J. R.
Izbicki and J. Sandoval and M. Esteller and K. Pantel and A.
Risch$^*$ and H. Wikman},
title = {{I}dentification of {HERC}5 and its potential role in
{NSCLC} progression.},
journal = {International journal of cancer},
volume = {136},
number = {10},
issn = {0020-7136},
address = {Bognor Regis},
publisher = {Wiley-Liss},
reportid = {DKFZ-2017-03834},
pages = {2264 - 2272},
year = {2015},
abstract = {For better lung cancer diagnosis and therapy, early
detection markers of tumor dissemination are urgently
needed, as most lung cancers do not show symptoms until
extensive metastasis formation has already taken place. Our
previous studies showed that in non-small cell lung cancer
(NSCLC) early tumor dissemination is associated with a loss
of chromosome 4q12-q32 and the presence of disseminated
tumor cells (DTC) in the bone marrow. In order to identify
the potential target gene in this region, a screen for
methylation-dependent expression was performed. Lung cancer
cell lines showing a loss of 4q as well as a normal
bronchial epithelial cell line as control were treated with
5-aza-2'-deoxycytidine (5-aza-CdR) followed by expression
profiling. Seven genes within the 4q target region, which
have been associated with a positive DTC status before were
found to be regulated by hypermethylation. QRT-PCR in an
independent sample set identified HERC5 as a potential
target gene. Quantitative methylation analysis of these lung
tissue samples revealed that HERC5 promoter hypermethylation
was significantly associated with positive DTC status (p =
0.020) and occurrence of brain metastases (p = 0.015). In
addition, hypermethylation of the HERC5 promoter in NSCLC
was identified as a predictor for poor survival for Stage I
adenocarcinoma patients (p = 0.022) and also for poor
overall survival in metastatic lung cancer patients (p =
0.028). In conclusion, HERC5 may function as a prognostic
marker and is associated with tumor dissemination in lung
cancer.},
keywords = {HERC5 protein, human (NLM Chemicals) / Intracellular
Signaling Peptides and Proteins (NLM Chemicals) / decitabine
(NLM Chemicals) / Azacitidine (NLM Chemicals)},
cin = {C060 / C010},
ddc = {610},
cid = {I:(DE-He78)C060-20160331 / I:(DE-He78)C010-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25353388},
doi = {10.1002/ijc.29298},
url = {https://inrepo02.dkfz.de/record/127812},
}