多发性内分泌肿瘤
多发性内分泌肿瘤2型
嗜铬细胞瘤
病理
错义突变
门1
生物
移码突变
胰腺
内分泌学
癌症研究
内科学
种系突变
医学
表型
突变
遗传学
基因
出处
期刊:PubMed
日期:1997-01-01
卷期号:81: 125-38
被引量:3
摘要
Multiple Endocrine Neoplasia (MEN) is an inherited syndrome which appears in two major forms referred to as type 1 (MEN-1) and type 2 (MEN-2). MEN-1 is characterized by the occurrence of neuroendocrine parathyroid, pancreas, duodenum and pituitary lesions. In addition to these tumors adrenocortical, lipomatous and neuroendocrine tumors in other locations may develop. The genetic defect of MEN-1 has recently been identified and involves a new form of tumor suppressor gene called mu on chromosome 11q13. It codes for a protein called menin which is expressed in a variety of human tissues and organs. In MEN-1 gene carriers inactivating germline frameshift, nonsense, missense and in-frame deletion mutations scattered throughout the 10 coding exons have been identified. The MEN-2 syndrome is divided into three clinical variants referred to as MEN-2A, MEN-2B and familial medullary thyroid carcinoma (FMTC) which share medullary thyroid carcinomas as part of the disease phenotype. In MEN-2A pheochromocytomas and parathyroid hyperplasia and in MEN-2B additional skeletal abnormalities and ganglioneuromatosis may also be encountered. All three MEN-phenotypes are associated with oncogenic point mutations of the RET protooncogene on chromosome 10q11.2 which encodes a receptor-type tyrosine kinase. Its ligand--the glial cell line derived neurotropic factor (GDNF)--forms a signaling complex with the alpha type of the GDNF receptor. All neuroendocrine tumors of the different MEN-phenotypes may also occur sporadically and there are only few clinical and pathomorphological features which are helpful to discriminate sporadic from MEN-associated neuroendocrine neoplasms. The recent achievements of molecular pathology now allow for the unambiguous identification of MEN gene carriers among patients with neuroendocrine neoplasms by DNA testing for mutations in the mu and RET gene. In this overview, distinct macroscopic and histopathological features of the two MEN phenotypes will be summarized and most recent findings on the molecular pathology of these syndromes will be outlined, together with molecular methods to identify disease-gene carriers.
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