Hannon Tamara S, King Denise Walker, Brinkman Abigail D, Steinmetz Rosemary, Davis Mary M, Eugster Erica A, Pescovitz Ora H
Department of Pediatrics, James Whitcomb Riley Hospital for Children, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis 46202, USA.
J Pediatr Endocrinol Metab. 2002;15 Suppl 3:891-5.
Activating mutations of the Gsalpha gene are responsible for McCune-Albright syndrome and have also been identified in sporadic tumors of the pituitary and thyroid. When associated with malignancy, activating Gsalpha mutations are known as gsp-oncogenes. We hypothesized that similar activating mutations might also account for some cases of premature thelarche and/ or granulosa cell tumors. Polymerase chain reaction and DNA sequencing was used to screen for activating mutations of Gsalpha genes in children with premature thelarche and in pathologic specimens from juvenile and adult granulosa cell tumors. Because these disorders involve over-activity of the FSH-signaling pathway, we also screened for activating mutations of the FSH receptor. No mutations were detected in either the Gsalpha or the FSHR fragment studied. Previously reported polymorphisms (Ser680Asn and Ala307Thr) of the FSHR were detected in 25/27 tumor samples and 9/9 premature thelarche samples. We conclude that activating mutations in previously identified mutation 'hot-spots' in the Gsalpha and FSH receptor genes are probably not a major cause of premature thelarche or granulosa cell tumors. In contrast, polymorphisms of the FSH receptor are common.
Gsα基因的激活突变是McCune-Albright综合征的病因，并且在垂体和甲状腺的散发性肿瘤中也已被发现。当与恶性肿瘤相关时，激活的Gsα突变被称为gsp癌基因。我们推测，类似的激活突变可能也是部分性早熟和/或颗粒细胞瘤病例的病因。采用聚合酶链反应和DNA测序技术，对性早熟儿童以及青少年和成人颗粒细胞瘤的病理标本进行Gsα基因突变筛查。由于这些疾病涉及促卵泡激素（FSH）信号通路的过度激活，我们还对FSH受体的激活突变进行了筛查。在所研究的Gsα或FSHR片段中均未检测到突变。在27份肿瘤样本中的25份以及9份性早熟样本中的9份中检测到了先前报道的FSHR多态性（Ser680Asn和Ala307Thr）。我们得出结论，Gsα和FSH受体基因中先前确定的突变“热点”中的激活突变可能不是性早熟或颗粒细胞瘤的主要病因。相比之下，FSH受体的多态性很常见。
