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• W2739067554 abstract "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.We isolated CK18positive 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).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), PAGhigh DTCs conferred an independent risk for a significantly decreased survival.The analysis of PAG/CIN in solitary marker-positive DTCs identifies operable EAC patients with poor prognosis, indicating a more aggressive minimal residual disease." @default.
• W2739067554 created "2017-07-31" @default.
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• W2739067554 date "2017-07-20" @default.
• W2739067554 modified "2023-10-15" @default.
• W2739067554 title "Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma" @default.
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• W2739067554 doi "https://doi.org/10.1038/bjc.2017.233" @default.
• W2739067554 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5572184" @default.
• W2739067554 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28728164" @default.
• W2739067554 hasPublicationYear "2017" @default.
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