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Status |
Public on Apr 01, 2009 |
Title |
An integromic analysis reveals that metaplastic carcinomas are distinct from basal-like tumors. |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. PIK3CA mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor-positive cancers (34.5%; P = 0.32), 17 of 75 HER-2-positive samples (22.7%; P = 0.04), 20 of 240 basal-like cancers (8.3%; P < 0.0001), and 0 of 14 claudin-low tumors (P = 0.004). Of 7 phosphatidylinositol 3-kinase/AKT pathway phosphorylation sites, 6 were more highly phosphorylated in MBCs than in other breast tumor subtypes. The majority of MBCs displayed mRNA profiles different from those of the most common, including basal-like cancers. By transcriptional profiling, MBCs and the recently identified claudin-low breast cancer subset constitute related receptor-negative subgroups characterized by low expression of GATA3-regulated genes and of genes responsible for cell-cell adhesion with enrichment for markers linked to stem cell function and epithelial-to-mesenchymal transition (EMT). In contrast to other breast cancers, claudin-low tumors and most MBCs showed a significant similarity to a "tumorigenic" signature defined using CD44(+)/CD24(-) breast tumor-initiating stem cell-like cells. MBCs and claudin-low tumors are thus enriched in EMT and stem cell-like features, and may arise from an earlier, more chemoresistant breast epithelial precursor than basal-like or luminal cancers. PIK3CA mutations, EMT, and stem cell-like characteristics likely contribute to the poor outcomes of MBC and suggest novel therapeutic targets.
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Overall design |
Comparison of reference samples against treatment
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Contributor(s) |
Hennessy BT, Perou CM, Mills GB |
Citation(s) |
19435916 |
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Submission date |
Mar 18, 2008 |
Last update date |
Nov 17, 2017 |
Contact name |
Charles M. Perou |
E-mail(s) |
cperou@med.unc.edu
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Organization name |
University of North Carolina at Chapel Hill
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Department |
Professor of Genetics, and Pathology & Laboratory Medicine; Lineberger Comprehensive Cancer Center
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Street address |
12-044 Lineberger Comprehensive Cancer Center CB# 7295
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City |
Chapel Hill |
State/province |
NC |
ZIP/Postal code |
27599-7264 |
Country |
USA |
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Platforms (4)
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GPL885 |
Agilent-011521 Human 1A Microarray G4110A (Feature Number version) |
GPL887 |
Agilent-012097 Human 1A Microarray (V2) G4110B (Feature Number version) |
GPL1390 |
Agilent Human 1A Oligo UNC custom Microarrays |
GPL5325 |
Agilent UNC Perou Lab Homo sapiens 1X44K Custom Array |
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Samples (244)
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Relations |
BioProject |
PRJNA107281 |