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E-GEOD-21217 - 18F-fluorodeoxy-glucose positron emission tomography marks MYC-overexpressing human basal-like breast cancers

Status
Released on 1 November 2011, last updated on 14 November 2011
Organism
Homo sapiens
Samples (33)
Arrays (2)
Protocols (8)
Description
Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.
Experiment type
transcription profiling by array 
Contacts
Nicolaos Jay Palaskas <geo@ncbi.nlm.nih.gov>, Adriana Heguy, Cameron Brennan, Carl Campos, Chris Sander, Chris Tran, Dan Rohle, Elisa Port, Evangelia Komisopoulou, Hong Wu, Ingo K Mellinghoff, Jason T Huse, Joseph R Osborne, Justin Wong, Michael E Phelps, Nicolaos Palaskas, Nikolaus Schultz, Richard Taschereau, Seema B Plaisier, Steven M Larson, Thomas G Graeber
Citation
18F-fluorodeoxy-glucose positron emission tomography marks MYC-overexpressing human basal-like breast cancers. Palaskas N, Larson SM, Schultz N, Komisopoulou E, Wong J, Rohle D, Campos C, Yannuzzi N, Osborne JR, Linkov I, Kastenhuber ER, Taschereau R, Plaisier SB, Tran C, Heguy A, Wu H, Sander C, Phelps ME, Brennan C, Port E, Huse JT, Graeber TG, Mellinghoff IK. , PMID:21646475
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-21217.idf.txt
Sample and data relationshipE-GEOD-21217.sdrf.txt
Raw data (1)E-GEOD-21217.raw.1.zip
Processed data (1)E-GEOD-21217.processed.1.zip
Array designsA-AFFY-33.adf.txt, A-AFFY-44.adf.txt
R ExpressionSetE-GEOD-21217.eSet.r
Links