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Series GSE63306 Query DataSets for GSE63306
Status Public on Feb 14, 2017
Title Recurrent aneuploidy patterns enable fitness gains in tumor metabolism
Organisms Homo sapiens; Mus musculus
Experiment type Genome variation profiling by genome tiling array
Summary Copy number alteration (CNA) profiling of human tumors has revealed recurrent patterns of DNA amplifications and deletions. These patterns are indicative of conserved selection pressures, but cannot be fully explained by known oncogenes and tumor suppressor genes. Using integrative analysis of CNA data from patient tumors and experimental systems, we report that principal component analysis-defined CNA signatures are predictive of glycolytic phenotypes, including FDG-avidity of patient tumors, and increased proliferation. The primary glycolysis-linked CNA signature is associated with p53 mutation and shows coordinate amplification of glycolytic genes and other cancer-linked metabolic enzymes including TIGAR and RPIA. In contrast, alternative signatures involve both different mechanisms of tumor suppression loss (eg, MDM2 amplification) and different glycolysis enzyme isoforms. Furthermore, a cross-species CNA comparison identified 21 conserved CNA regions, containing 13 enzymes in the glycolysis and pentose phosphate pathways in addition to known cancer driving genes. In validation experiments, exogenous expression of hexokinase and enolase enzymes resulted in reduced propensities for amplifications at the corresponding endogenous loci. Our findings support metabolic stress as a selective pressure underlying the recurrent CNAs observed in human tumors, and further cast genomic instability as an enabling event in tumorigenesis and metabolic evolution.
 
Overall design (i) There are 54 unique CD1 MEF sublines and 71 total CD1 MEF samples, including control diploid sample profiled at passage 1 and replicates of samples profiled at more than one passage. There is 1 DR4 MEF subline profiled at two different passages and 1 DR4 MEF diploid control sample profiled at passage 1. There are 29 unique p53-/- MEF sublines and 37 total MEF samples, including control diploid p53+/+ sample profiled at passage 2 and replicates of samples profiled at more than one passage.
(ii) 10 human breast cancer samples were profiled on Agilent 244K aCGH arrays per manufacturer's instructions. Either matched normal DNA or a pooled reference normal DNA was used as the reference. The 10 aCGH samples are related to both this study and to GSE21217. *** Raw data are unavailable ****
 
Contributor(s) Graham NA, Minasyan A, Lomova A, Zhao S, Delgado A, Chan S, Friedman M, Palaskas N, Mellinghoff IK, Larson SM, Port E, Hurtz C, Ng C, Qiao R, Wu H, Müschen M, Graeber TG
Citation(s) 28202506
Submission date Nov 14, 2014
Last update date Feb 17, 2017
Contact name Thomas G. Graeber
E-mail(s) TGraeber@mednet.ucla.edu
Organization name UCLA
Department Mol & Med Pharmacology
Lab Graeber
Street address 570 Westwood Plaza, Bldg 114, Room 4341 CNSI
City Los Angeles
State/province CA
ZIP/Postal code 90095-7227
Country USA
 
Platforms (2)
GPL4091 Agilent-014693 Human Genome CGH Microarray 244A (Feature number version)
GPL10449 Agilent-027411 SurePrint G3 Mouse CGH Microarray 4x180K (Feature Number version)
Samples (121)
GSM1545370 Wild type CD1 mouse embryonic fibroblast subline C9 rep.2
GSM1545371 Wild type CD1 mouse embryonic fibroblast subline H1 rep.3
GSM1545372 Wild type CD1 mouse embryonic fibroblast subline H1 rep.2
Relations
BioProject PRJNA267244

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
GSE63306_RAW.tar 5.3 Gb (http)(custom) TAR (of TXT)
GSE63306_brca_hg19_seg.mean.seg.txt.gz 30.9 Kb (ftp)(http) TXT
GSE63306_processed_data_seg.mean.seg.txt.gz 261.6 Kb (ftp)(http) TXT
Processed data are available on Series record
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