Genetics and Biology of Pheochromocytoma
Genetics and Biology of Pheochromocytoma
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嗜铬细胞瘤的遗传学和生物学
DOI：
--
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发表时间：
2007
影响因子：
1.8
通讯作者：
G. Parenti
中科院分区：
文献类型：
--
作者：
M. Mannelli;L. Simi;M. S. Gaglianò;G. Opocher;T. Ercolino;L. Becherini;G. Parenti
嗜铬细胞瘤的家族性形式最近被证明比过去认为的更常见。目前已知负责肿瘤形成的基因是RET、VHL、NF 1、SDHB、SDHC和SDHD。这些基因的生殖系突变增加了发生嗜铬细胞瘤和/或副神经节瘤的风险，这些肿瘤与其他肿瘤相关，并分别表征了不同的临床综合征，如MEN 2、von Hippel-Lindau（VHL）和1型神经纤维瘤病（NF 1）或PGL综合征。虽然嗜铬细胞瘤/副神经节瘤形成的发病机制在很大程度上仍然是未知的，但对家族性形式的研究已经开始揭示一些有利于肿瘤形成的途径，如酪氨酸激酶的激活、缺氧诱导因子的诱导、癌基因Ras的激活或细胞凋亡的减少。这些研究还表明，各种基因突变可以不同地影响嗜铬细胞瘤的生物学特性：例如，虽然肿瘤在MEN 2中主要是肾上腺素能的（肾上腺素分泌）和肾上腺素分泌，但在VHL中主要是去甲肾上腺素能的（去甲肾上腺素分泌）和持续分泌。在PGL综合征中也可以观察到生物学变异性，其中肿瘤在头部和颈部发展，并且起源于副交感神经并且不分泌，或者在胸部和腹部发展，其中它们起源于交感神经并且分泌儿茶酚胺。目前，强烈建议对嗜铬细胞瘤或副神经节瘤患者进行基因检测，对于年轻患者或多发性或复发性肿瘤患者是强制性的。肿瘤的临床表现和生物学特征可能会提示首先测试的基因的优先级。
The familial forms of pheochromocytoma have recently been demonstrated to be more frequent than believed in the past. The genes currently known to be responsible for tumor formation are RET, VHL, NF1, SDHB, SDHC and SDHD. Germline mutations of these genes increase the risk of developing pheochromocytomas and/or paragangliomas which variably associate with other neoplasms and characterize diverse clinical syndromes such as MEN 2, von Hippel-Lindau (VHL), and neurofibromatosis type 1 (NF 1), or the PGL syndromes, respectively. Although the pathogenesis of pheochromocytoma/paraganglioma formation is still largely unknown, studies of the familial forms have started to uncover some pathways that favor tumor formation, such as activation of tyrosine-kinase, induction of hypoxia-inducible factors, activation of the oncogene Ras or reduced apoptosis. These studies have also demonstrated that various gene mutations can differently affect the biological characteristics of pheochromocytoma: for example, while the tumors are mostly adrenergic (epinephrine secreting) and episodically secreting in MEN 2, they are mostly noradrenergic (norepinephrine secreting) and continuously secreting in VHL. Biological variability can also be observed in the PGL syndromes where tumors develop in the head and neck and are parasympathetic in origin and non-secreting, or in the thorax and the abdomen, where they are sympathetic in origin and catecholamine secreting. Genetic testing in patients with pheochromocytomas or paragangliomas is, at present, strongly recommended and is mandatory in young patients or in cases of multiple or recurrent tumors. The clinical picture and the biological characteristics of the tumor may suggest the priority of the genes to be tested first.
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影响因子：
50.3
作者：
Lee, S;Nakamura, E;Schlisio, S
通讯作者：
Schlisio, S
DOI：
10.1073/pnas.95.20.11715
发表时间：
1998-09-29
影响因子：
11.1
作者：
Chandel, NS;Maltepe, E;Schumacker, PT
通讯作者：
Schumacker, PT
影响因子：
56.9
作者：
Baysal, BE;Ferrell, RE;Devlin, B
通讯作者：
Devlin, B
影响因子：
3.5
作者：
DONISKELLER, H;DOU, SS;WELLS, SA
通讯作者：
WELLS, SA