Dataset Information

Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma.

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 CIN^high 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.

SUBMITTER: Schumacher S

PROVIDER: S-EPMC5572184 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma.

Schumacher Sarah S Bartenhagen Christoph C Hoffmann Martin M Will Daniel D Fischer Johannes C JC Baldus Stephan E SE Vay Christian C Fluegen Georg G Dizdar Levent L Vallböhmer Daniel D Klein Christoph A CA Knoefel Wolfram T WT Stoecklein Nikolas H NH Möhlendick Birte B

British journal of cancer 20170720 5

<h4>Background</h4>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 CIN<sup>high</sup> DTCs on prognosis.<h4>Methods</h4>We isolated CK18<sup>positive</sup> DTCs from bone marrow (BM) or lymph node (LN) preparations of operable EAC patients ...[more]

PMID: 28728164

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Dataset Information

Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma.

Background

Methods

Results

Conclusions

Publications

Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma.

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