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Series GSE45565 Query DataSets for GSE45565
Status Public on Apr 19, 2013
Title Clonal evolution, genomic drivers, and effects of therapy in chronic lymphocytic leukemia
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary The identification of gene mutation and structural genomic aberrations that are critically involved in CLL pathogenesis is still evolving. One may postulate that genomic driver lesions with effects on CLL proliferation, apoptosis thresholds, or chemotherapy resistance should increase in frequency over time when measured sequentially in a large CLL cohort. We sequentially sampled a large, well-characterized CLL cohort at a mean of 4 years between samplings. The paired analysis included 156 patients, of whom 114 remained untreated and 42 received intercurrent therapies. Results: we identify a strong effect of intercurrent therapies on the frequency of acquisition of aCNAs in CLL. Importantly, the spectrum of acquired genomic changes was largely similar in patients that did or did not receive intercurrent therapies; therefore, various genomic changes that become part of the dominant clones are often already present in CLL cell populations prior to therapy. Further, we provide evidence that therapy of CLL with preexisting TP53 mutations results in the outgrowth of genomically very complex clones which dominate at relapse.
Using complementary technologies directed at the detection of genomic events that are present in substantial proportions of of the clinically relevant CLL disease bulk, we capture aspects of genomic evolution in CLL over time, including increases in the frequency of genomic complexity, specific recurrent aCNAs, and TP53 mutations.
Overall design Data from 156 paired samples (enrollment and one longitudinal sample) are included in this data set. Of these, 27 patients were assayed at two (or, rarely, more than two) time points. Please note: normal DNA and enrollment date tumor DNA CEL files and SNP call files will be found in a separate GEO data submission: GSE30777
Contributor(s) Ouillette PD, Saiya-Cork K, Seymour E, Li C, Shedden K, Malek SN
Citation(s) 23620403
Submission date Mar 27, 2013
Last update date Nov 27, 2018
Contact name Sami N Malek
Phone 734-763-1222
Organization name University of Michigan
Department Internal Medicine, Hematology-Oncology
Street address 4410 Cancer Center; 1500 E Medical Center Dr
City Ann Arbor
State/province MI
ZIP/Postal code 48109
Country USA
Platforms (1)
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
Samples (496)
GSM764339 primary human: blood; FACS-sorted CD3+ cells (CLL001N_CD3)
GSM764340 primary human: blood; FACS-sorted CD19+ cells (CLL001T)
GSM764341 primary human: buccal swab (CLL002N)
BioProject PRJNA195404

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
GSE45565_RAW.tar 14.1 Gb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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