Hypoxia Pathway Mutations in Pheochromocytomas and Paragangliomas.
Cytogenet Genome Res
; 150(3-4): 227-241, 2016.
Article
en En
| MEDLINE
| ID: mdl-28231563
Pheochromocytomas (PCC) and sympathetic paragangliomas (PGL) are rare neuroendocrine tumors, which derive from chromaffin cells occurring in the adrenal medulla and extra-adrenal sympathetic paraganglia. PCC and PGL are often benign, catecholamine-producing tumors, responsible for a myriad of symptoms that may be potentially hazardous to the patient. In contrast, nonsecreting parasympathetic PGL, derived from chief cells, develop mainly in the head and neck region. Although PCC/PGL are more commonly sporadic tumors, germline mutations are present in up to 40% of the patients, ranking these tumors among those with the highest degree of heritability. PCC/PGL are associated with a variety of hereditary syndromes, comprising genetic alterations in RET, NF1, VHL, and SDHx genes, the last 2 being involved in regulating the hypoxia pathway. Additional hypoxia pathway-related genes have been recently associated with PCC/PGL development, namely EGLN1 and EPAS1. Thus, dysregulation of the hypoxia pathway seems to play a major role in PCC/PGL development, in particular through the stabilization of hypoxia-inducible factors and the appearance of a pseudohypoxia signature. This article is focused on reviewing the tumorigenic mechanisms resultant from VHL, SDHx, EGLN1, and EPAS1 mutations, as well as the associated tumors, namely PCC/PGL, and extra manifestations such as polycythemia. In the light of the recent discoveries, hypoxia pathway molecules appear as key players in PCC/PGL development.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Paraganglioma
/
Feocromocitoma
/
Hipoxia de la Célula
/
Mutación
Límite:
Humans
Idioma:
En
Revista:
Cytogenet Genome Res
Asunto de la revista:
GENETICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Portugal
Pais de publicación:
Suiza