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Series GSE83566 Query DataSets for GSE83566
Status Public on Aug 25, 2017
Title Frequent Evolution of Copy Number Alterations Following First‑line Treatment with FC(R) is Enriched with TP53 Alterations which Impact Long Term Survival – Results from the CLL8 Trial
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
SNP genotyping by SNP array
Summary To define clonal evolution of somatic copy number alterations (CNAs) in chronic lymphocytic leukemia (CLL), sequential samples of 103 individuals were investigated by SNP-array analysis for appearance of novel CNAs. Patients were enrolled on the CLL8 trial and uniformly received fludarabine, cyclophosphamide +/- rituximab (FC/FCR). Comparing two sequential samples prior to therapy (N=27, a median of 2.9 years apart), CNA evolution occurred in 19% of cases. In contrast, when comparing treatment‑initiation and relapse genomic profiles (a median of 3.6 years apart), CNA evolution was seen in 40% of cases. This suggested association of FC(R) treatment with higher rate of CNA evolution. The only clinical feature significantly associated with CNA evolution was FCR therapy compared with FC (OR=2.806, p=0.024). As this might be related to narrower evolutionary bottlenecks imposed by the more effective FCR therapy, which could execute more selection pressure, we examined matched minimal residual disease data. We found CNA evolution more frequently in cases with CLL cell numbers rapidly receding in early phases of treatment. Finally, we observed frequent rises of TP53 mutant/deficient clones with therapy (N=19, 22%) that were associated with decreased overall survival (p=0.016). These results demonstrated that re-examination of TP53 status upon relapse provides important information.
 
Overall design Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic peripheral blood samples.
Copy number analysis of Affymetrix® 6.0 arrays was performed for 216 CLL samples. There are also 52 samples from mononuclear cells negative for CD19 which were taken at treatment-initiation and used as references for copy number inference.
 
Citation(s) 27909343
Submission date Jun 21, 2016
Last update date Nov 27, 2018
Contact name Jennifer Edelmann
E-mail(s) j.edelmann@qmul.ac.uk
Phone 0041 (0)20 7882 8780
Organization name Barts Cancer Institute
Department Centre for Haemato-/Oncology
Lab 3rd Floor John Vane Science Centre
Street address Charterhouse Square
City London
ZIP/Postal code EC1M 6BQ
Country United Kingdom
 
Platforms (1)
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
Samples (268)
GSM2208976 Chronic lymphocytic leukemia 1 pre treatment
GSM2208977 Chronic lymphocytic leukemia 1 first treatment
GSM2208978 Chronic lymphocytic leukemia 1 paired normal
Relations
BioProject PRJNA326400

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE83566_CLL8_CNAevolution_cytonorm.txt.gz 2.1 Gb (ftp)(http) TXT
GSE83566_RAW.tar 10.7 Gb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file
Processed data are available on Series record
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