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@ARTICLE{Steinert:128376,
author = {G. Steinert and S. Schölch and T. Niemietz and N. Iwata
and S. A. García and B. Behrens and A. Voigt and M.
Kloor$^*$ and A. Benner$^*$ and U. Bork and N. N. Rahbari
and M. W. Büchler and N. H. Stoecklein and J. Weitz and M.
Koch},
title = {{I}mmune escape and survival mechanisms in circulating
tumor cells of colorectal cancer.},
journal = {Cancer research},
volume = {74},
number = {6},
issn = {1538-7445},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2017-04393},
pages = {1694 - 1704},
year = {2014},
abstract = {The prognosis of colorectal cancer is closely linked to the
occurrence of distant metastases. Systemic dissemination is
most likely caused by circulating tumor cells (CTC). Despite
the fundamental role of CTC within the metastatic cascade,
technical obstacles have so far prevented detailed genomic
and, in particular, phenotypic analyses of CTC, which may
provide molecular targets to delay or prevent distant
metastases. We show here a detailed genomic analysis of
single colorectal cancer-derived CTC by array comparative
genomic hybridization (aCGH), mutational profiling, and
microsatellite instability (MSI) analysis. Furthermore, we
report the first gene expression analysis of manually
selected colorectal cancer-derived CTC by quantitative
real-time PCR (qRT-PCR) to investigate transcriptional
changes, enabling CTC to survive in circulation and form
distant metastases. aCGH confirmed the tumor cell identity
of CellSearch-isolated colorectal cancer-derived CTC.
Mutational and MSI analyses revealed mutational profiles of
CTC to be similar, but not identical to the corresponding
tumor tissue. Several CTC exhibited mutations in key genes
such as KRAS or TP53 that could not be detected in the
tumor. Gene expression analyses revealed both a pronounced
upregulation of CD47 as a potential immune-escape mechanism
and a significant downregulation of several other pathways,
suggesting a dormant state of viable CTC. Our results
suggest mutational heterogeneity between tumor tissue and
CTC that should be considered in future trials on targeted
therapy and monitoring of response. The finding of
upregulated immune-escape pathways, which may be responsible
for survival of CTC in circulation, could provide a
promising target to disrupt the metastatic cascade in
colorectal cancer. Cancer Res; 74(6); 1694-704. ©2014
AACR.},
cin = {G105 / C060},
ddc = {610},
cid = {I:(DE-He78)G105-20160331 / I:(DE-He78)C060-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24599131},
doi = {10.1158/0008-5472.CAN-13-1885},
url = {https://inrepo02.dkfz.de/record/128376},
}