Schumacher, Sarah and Bartenhagen, Christoph and Hoffmann, Martin and Will, Daniel and Fischer, Johannes C. and Baldus, Stephan E. and Vay, Christian and Fluegen, Georg and Dizdar, Levent and Vallboehmer, Daniel and Klein, Christoph A. and Knoefel, Wolfram T. and Stoecklein, Nikolas H. and Moehlendick, Birte (2017) Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma. BRITISH JOURNAL OF CANCER, 117 (5). pp. 725-733. ISSN 0007-0920, 1532-1827
Full text not available from this repository. (Request a copy)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: | Article |
|---|---|
| Uncontrolled Keywords: | MINIMAL RESIDUAL CANCER; COPY NUMBER ALTERATIONS; LYMPH-NODE METASTASES; CHROMOSOMAL INSTABILITY; BREAST-CANCER; BARRETTS-ESOPHAGUS; BONE-MARROW; DIAGNOSTIC LEUKAPHERESIS; GENETIC-ANALYSIS; LUNG-CANCER; disseminated tumour cells; single cell analysis; minimal residual disease; oesophageal cancer; chromosomal instability; heterogeneity; copy number alteration; prognosis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:16 |
| Last Modified: | 25 Feb 2019 13:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1369 |
Actions (login required)
 |
View Item |
