Molecular and cellular biology of pheochromocytomas and extra-adrenal paragangliomas.
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| Abstract |
Efforts to understand the pathobiology of pheochromocytomas and extra-adrenal paragangliomas have been spurred by genetic and gene expression profiling studies showing genotype-phenotype correlations in familial pheochromocytoma/paraganglioma syndromes and in some sporadic tumors. The current challenge is to relate catalogs of genetic and phenotypic markers to cell biology. Hypothetical bases for genotype-phenotype correlations include: cell of origin, pathway dependence, and functional and anatomic context. A further consideration is phenotype plasticity. Cross talk between signaling pathways provides a general framework for understanding how mutations of apparently unrelated genes might lead to the same type of tumor, and also suggests that targeted therapies might be directed either at a specific mutated gene or a downstream signal transducer. However, precise mechanisms of tumorigenesis remain unknown. An intriguing hypothesis proposes that mutations of RET, NF1, VHL, or SDH predispose to hereditary pheochromocytoma/ paraganglioma by causing defective apoptotic culling of cells that would normally be destroyed during embryogenesis. An argument favoring survival rather than mitogenesis as a common denominator is that the same mutations are rare in sporadic pheochromocytomas/paragangliomas, suggesting they only need to act during a limited developmental window. An implication is that tumor precursors could be identified and eradicated in individuals who carry the mutations.
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| Authors | Arthur S Tischler |
| Journal | Endocrine pathology (Endocr Pathol) Vol. 17 Issue 4 Pg. 321-8 ( 2006) ISSN: 1046-3976 [Print] United States |
| PMID | 17525480 (Publication Type: Journal Article, Review) |
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