BRAF and endocrine tumors:: mutations are frequent in papillary thyroid carcinomas, rare in endocrine tumors of the gastrointestinal tract and not detected in other endocrine tumors
BRAF and endocrine tumors:: mutations are frequent in papillary thyroid carcinomas, rare in endocrine tumors of the gastrointestinal tract and not detected in other endocrine tumors
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DOI：
10.1677/erc.1.00841
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发表时间：
2004-12-01
影响因子：
3.9
通讯作者：
Komminoth, P
中科院分区：
文献类型：
--
作者：
Perren, A;Schmid, S;Komminoth, P
散发性内分泌肿瘤的发生机制尚未完全清楚。位于7 q34上的丝氨酸/苏氨酸激酶基因BRAF的激活点突变在广泛的恶性肿瘤中被发现，其中最高频率（66%）发生在恶性黑素瘤中。黑色素瘤是神经嵴衍生细胞的肿瘤，如甲状腺髓样癌、嗜铬细胞瘤和副神经节瘤。BRAF尚未在弥漫性神经内分泌系统或神经嵴源性细胞的内分泌肿瘤中进行检查。我们检查了130例胰腺、甲状旁腺、肾上腺髓质、副神经节、肺和胃肠道内分泌肿瘤以及滤泡和C细胞源性甲状腺肿瘤。我们发现甲状腺乳头状癌中V559 E突变率很高（47%），分化良好的胃内分泌癌（恶性类癌）中有一个V599 E突变，但在所有其他内分泌肿瘤中没有激活BRAF突变。这些结果指向不同的内分泌肿瘤的肿瘤发生的不同途径的各种定位和只有罕见的参与的MAP激酶（MAPK）途径的一个子集的恶性神经内分泌肿瘤。
The tumorigenesis of sporadic endocrine tumors is still not fully understood. Activating point mutations of the serine/threonine kinase gene BRAF located on 7q34 are found in a wide range of malignancies, with the highest frequency (66%) occurring in malignant melanomas. Melanomas are tumors of neural-crest-derived cells as are medullary thyroid carcinomas, pheochromocytomas and paragangliomas. BRAF has not been examined in endocrine tumors of the diffuse neuroendocrine system or of neural-crest-derived cells.We examined 130 endocrine tumors of the pancreas, parathyroid gland, adrenal medulla, paraganglia, lung and gastrointestinal tract as well as follicular and c-cell-derived thyroid tumors. We found a high rate of V559E mutations in papillary thyroid carcinomas (47%), one V599E mutation in a well-differentiated gastric endocrine carcinoma (malignant carcinoid), but no activating BRAF mutations in all other endocrine tumors examined. These results point towards different pathways in tumorigenesis of endocrine tumors of various localizations and only rare involvement of the MAP kinase (MAPK) pathway in a subset of malignant neuroendocrine tumors.