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| Status |
Public on Aug 12, 2005 |
| Title |
Expression Profiling of pheochromocytomas of various genetic origins |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes: RET, VHL, NF1, and subunits B, C and D of succinate dehydrogenase (SDH). The proteins encoded by these multiple genes regulate distinct functions. To identify molecular interactions between the distinct pathways we performed expression profiling of a large cohort of pheochromocytomas. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1?. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1? activity in tumors.
Keywords: disease state analysis: Primary sporadic and hereditary pheochromocytomas and paragangliomas
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| Overall design |
We performed comparative analysis of expression profiling of 76 Pheochromocytomas and paragangliomas with a variety of mutations representatives of distinct pheochromocytoma susceptibility syndromes,sporadic tumors and familial tumors without an identifiable mutation. Six tumors were processed in duplicate.
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| Contributor(s) |
Dahia PL, Ross KN, Wright ME, Hayashida CY, Santagata S, Barontini M, Kung AL, Sanso G, Powers JF, Tischler AS, Hodin R, Heitritter S, Moore F Jr, Dluhy R, Sosa J, Tolgay Ocal I, Benn DE, Marsh DJ, Robinson BG, Schneider K, Garber J, Arum SM, Korbonits M, Grossman A, Pigny P, Toledo SP, Nosé V, Li C, Stiles CD |
| Citation(s) |
16103922 |
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| Submission date |
Jun 27, 2005 |
| Last update date |
Aug 10, 2018 |
| Contact name |
Patricia L. Dahia |
| E-mail(s) |
[email protected]
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| Phone |
210 5674866
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| Organization name |
UTHSCSA
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| Department |
Medicine/Cel&Struct Biology
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| Street address |
7703 Floyd Curl Dr MC7880
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| City |
San Antonio |
| State/province |
TX |
| ZIP/Postal code |
78229 |
| Country |
USA |
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| Platforms (1) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
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| Samples (76)
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| Relations |
| BioProject |
PRJNA92477 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE2841_RAW.tar |
247.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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