Boikos Sosipatros A, Stratakis Constantine A
Section on Endocrinology and Genetics (SEGEN), Developmental Endocrinology Branch (DEB), National Institute of Child Health and Human Development (NICHD), National Institues of Health, Bethesda, MD 20892-1103, USA.
Hum Mol Genet. 2007 Apr 15;16 Spec No 1:R80-7. doi: 10.1093/hmg/ddm019.
Pituitary tumors are among the most common human neoplasms. Although these common lesions rarely become clinically manifest and they are almost never malignant, they are the cause of significant morbidity in affected patients. The genetic causes of common pituitary tumors remain for the most part unknown; progress has been limited to the elucidation of the molecular etiology of four genetic syndromes predisposing to pituitary neoplasias: McCune-Albright syndrome, multiple endocrine neoplasia type 1, Carney complex and, most recently, familial acromegaly and prolactinomas and other tumors caused by mutations in the GNAS, menin, PRKAR1A, AIP, and p27 (CDKN1B) genes, respectively. Intense molecular studies of sporadic pituitary tumors from patients with negative family histories and no other neoplasms have yielded interesting findings with abnormalities in growth factor expression and cell cycle control dysregulation. To add to the difficulties in understanding pituitary tumorigenesis in man, good murine models of these neoplasms simply do not exist: pituitary tumors are common in rodents, but their histologic origin (mostly from the intermediate lobe), age of presentation (late in murine life) and clinical course make them hardly models of their human counterparts. The present report reviews the clinical and molecular genetics of the cAMP-dependent protein kinase pathway in human pituitary tumors; it also reviews briefly other pathways that have been involved in sporadic pituitary neoplasms. At the end, we attempt a unifying hypothesis for pituitary tumorigenesis, taking into account data that are also discussed elsewhere in this issue.
垂体肿瘤是人类最常见的肿瘤之一。尽管这些常见病变很少出现临床症状，且几乎从不恶变，但它们却是导致患者出现严重发病情况的原因。常见垂体肿瘤的遗传病因在很大程度上仍不清楚；目前的进展仅限于阐明四种易患垂体肿瘤的遗传综合征的分子病因：McCune - Albright综合征、1型多发性内分泌腺瘤病、Carney综合征，以及最近发现的家族性肢端肥大症和催乳素瘤，还有分别由GNAS、menin、PRKAR1A、AIP和p27（CDKN1B）基因突变引起的其他肿瘤。对家族史阴性且无其他肿瘤的患者的散发性垂体肿瘤进行的深入分子研究，已经得出了一些有趣的发现，即生长因子表达异常和细胞周期调控失调。更增加了理解人类垂体肿瘤发生机制难度的是，根本不存在合适的这类肿瘤的小鼠模型：垂体肿瘤在啮齿动物中很常见，但它们的组织学起源（大多来自中间叶）、出现的年龄（在小鼠生命后期）和临床过程使其很难成为人类垂体肿瘤的模型。本报告回顾了人类垂体肿瘤中cAMP依赖性蛋白激酶途径的临床和分子遗传学；还简要回顾了其他与散发性垂体肿瘤有关的途径。最后，我们尝试提出一个关于垂体肿瘤发生的统一假说，同时考虑到本期其他地方也讨论过的数据。
