[Pathogenic patterns of genetic predisposition to endocrine tumors].
Multiple endocrine neoplasia (MEN) are major predisposition syndromes to endocrine tumours and are characterised by an autosomal dominant disorder and full penetrance. MEN-1 is a major form of hyperparathyroidism associated with a high prevalence of endocrine tumours of the pancreas, pituitary gland, adrenal cortex and the lymphoid and bronchial endocrine tissues. MEN-2 is the familial syndrome of medullary thyroid carcinoma, associated with pheochromocytoma and hyperparathyroidism. Apart from the clinical expression of their allelic variants, both syndromes are different in their physiopathogenesis, in that MEN-2 is related to the constitutional activation of the proto-oncogene RET that encodes a putative tyrosine kinase receptor, while MEN-1 is a tumour suppressor gene model, related to mutations in the menin adapter-protein of multiple intracellular functions. The study of other rarer forms of predisposition to endocrine tumours, and especially to hyperparathyroidism, has uncovered new genes such as HRPT2, which show that multiple physiological routes, including the close regulation of transcription and genetic stability, may lead to the same clinical outcome. These hereditary models of endocrine cancer contribute as much to further physiopathogenic knowledge as to the therapeutic recommendations for managing these syndromes.
Calender
Alain
A
Service de génétique moléculaire et médicale, hôpital Edouard-Herriot, bâtiment B7, 5, place d'Arsonval, 69437 Lyon 03, France. alain.calender@chu-lyon.fr
D004701:Endocrine Gland Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics; D000090063:Proto-Oncogene Mas