Universität zu Köln

Schumacher, Sarah, Bartenhagen, Christoph, Hoffmann, Martin, Will, Daniel, Fischer, Johannes C., Baldus, Stephan E., Vay, Christian, Fluegen, Georg, Dizdar, Levent, Vallboehmer, Daniel, Klein, Christoph A. ORCID: 0000-0001-7128-1725, Knoefel, Wolfram T., Stoecklein, Nikolas H. and Moehlendick, Birte (2017). Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma. Br. J. Cancer, 117 (5). S. 725 - 734. LONDON: NATURE PUBLISHING GROUP. ISSN 1532-1827

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Abstract

Background: Chromosomal instability (CIN) has repeatedly been identified as a prognostic marker. Here we evaluated the percentage of aberrant genome per cell (PAG) as a measure of CIN in single disseminated tumour cells (DTC) isolated from patients with operable oesophageal adenocarcinoma (EAC), to assess the impact of CINhigh DTCs on prognosis. Methods: We isolated CK18(positive) DTCs from bone marrow (BM) or lymph node (LN) preparations of operable EAC patients. After whole-genome amplification, single DTCs were analysed for chromosomal gains and losses using metaphase-based comparative genomic hybridisation (mCGH). We calculated the PAG for each DTC and determined the critical threshold value that identifies high-risk patients by STEPP (Subpopulation Treatment Effect Pattern Plot) analysis in two independent EAC patient cohorts (cohort #1, n = 44; cohort # 2; n = 29). Results: The most common chromosomal alterations observed among the DTCs were typical for EAC, but the DTCs showed a varying PAG between individual patients. Generally, LNDTCs displayed a significantly higher PAG than BMDTCs. STEPP analysis revealed an increasing PAG of DTCs to be correlated with an increased risk for short survival in two independent EAC cohorts as well as in the corresponding pooled analysis. In all three data sets (cohort # 1, cohort # 2 and pooled cohort), PAG(high) DTCs conferred an independent risk for a significantly decreased survival. Conclusions: The analysis of PAG/CIN in solitary marker-positive DTCs identifies operable EAC patients with poor prognosis, indicating a more aggressive minimal residual disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schumacher, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartenhagen, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Will, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Johannes C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baldus, Stephan E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vay, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Fluegen, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Dizdar, Levent UNSPECIFIED UNSPECIFIED UNSPECIFIED Vallboehmer, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Christoph A. UNSPECIFIED orcid.org/0000-0001-7128-1725 UNSPECIFIED Knoefel, Wolfram T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoecklein, Nikolas H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moehlendick, Birte UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-221574
DOI:	10.1038/bjc.2017.233
Journal or Publication Title:	Br. J. Cancer
Volume:	117
Number:	5
Page Range:	S. 725 - 734
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1532-1827
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COPY NUMBER ALTERATIONS; LYMPH-NODE METASTASES; CHROMOSOMAL INSTABILITY; BONE-MARROW; DIAGNOSTIC LEUKAPHERESIS; BARRETTS-ESOPHAGUS; GENETIC-ANALYSIS; CANCER; EVOLUTION; PROGRESSION Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22157