Clonality analyses of adrenal medullary proliferations

2012-12-12T23:01:52Z (GMT) by Salvador J. Diaz-Cano
<p>Clonality remains as the hallmark of neoplasms. A dual genetic approach using markers non-related (e.g., X-chromosome inactivation assays) and related with the malignant transformation (such as loss of heterozygosity analyses of tumor suppressor genes) would provide useful clonality information from early and advanced tumor stages, respectively. Tumor progression and clonal selection would result in genetic instability and heterogeneous expression of those molecular markers related with the malignant pathway. Therefore, only the coexistence of multiple genetic abnormalities would support the clonal nature as an expression of convergent cell selection. Considering those facts, the currently available evidences on tumorigenesis and clonality in the adrenal medulla can be summarized in: (1) Multistep tumorigenesis defines the evolution of pheochromocytomas, as evidenced by the presence of several genetic alterations. (2) Both the significant association of non-random genetic alterations (specially 1p and 22q interstitial deletions) and the topographic accumulation of genetic deletions at the peripheral tumor compartment support a convergent clone selection for these neoplasms. (3) Although many genetic loci show non-random abnormalities, the most frequently involved locates on chromosome 1p regardless of genetic tumor background (sporadic or inherited predisposition). (4) Most pheochromocytomas should begin as monoclonal proliferations that does not always correlate with histopathologic features, particularly in inherited tumor syndromes. (5) Early histopathologic stages, described as adrenal medullary hyperplasias, are defined by hyperproliferative features in animal models and monoclonal patterns in the adrenal nodules from patients with MEN-2A.</p>
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