Oikonomou Eftychia, Barreto Diele C, Soares Beatriz, De Marco Luiz, Buchfelder Michael, Adams Eric F
School of Health and Life Sciences, Biomedical Chemistry Research Group, Aston University, Birmingham, B4 7ET, UK.
J Neurooncol. 2005 Jul;73(3):205-9. doi: 10.1007/s11060-004-5232-z.
Craniopharyngiomas and pituitary adenomas are both tumors of the hypothalamic and pituitary region, respectively that are frequently associated with endocrine defects either because of direct involvement of hormone producing cells (most pituitary tumors) or because of secondary defects due to disturbance of hypothalamic function (some pituitary tumors and craniopharyngiomas). Some studies suggest that mutant beta-catenin gene cells in craniopharyngiomas and pituitary adenomas contribute to their tumorigenesis. DNA was extracted from 73 cranial tumors and subjected to polymerase chain reaction (PCR) with previously described primers encompassing glycogen synthase kinase-3beta phosphorylation sites of the beta-catenin gene. Sequenced PCR products for possible beta-catenin gene mutations showed a total of 7/43 alterations in adamantinomatous craniopharyngioma-derived DNA samples. Two previously described beta-catenin mutations in codon 33 TCT(Ser) > TGT(Cys) and codon 37 TCT(Ser) > TTT(Phe), whereas three novel mutations in codon 41 ACC(Thr) > ATC(Ile), codon 33 TCT(Ser) > TAT(Tyr) and codon 32 GAC(Asp) > AAC(Asn) were observed. None of the 22 pituitary adenomas and the eight papillary craniopharyngiomas analyzed presented any sequence alterations. These findings demonstrate an association between beta-catenin gene alterations and craniopharyngiomas of the adamantinomatous type. Since this gene product is involved with development, these results suggest that beta-catenin mutations may contribute to the initiation and subsequent growth of congenital craniopharyngiomas.
颅咽管瘤和垂体腺瘤分别是下丘脑和垂体区域的肿瘤，它们常与内分泌缺陷相关，这要么是由于激素产生细胞直接受累（大多数垂体肿瘤），要么是由于下丘脑功能紊乱导致的继发性缺陷（一些垂体肿瘤和颅咽管瘤）。一些研究表明，颅咽管瘤和垂体腺瘤中的β-连环蛋白基因突变细胞有助于其肿瘤发生。从73例颅脑肿瘤中提取DNA，并使用先前描述的包含β-连环蛋白基因糖原合酶激酶-3β磷酸化位点的引物进行聚合酶链反应（PCR）。对可能的β-连环蛋白基因突变的PCR产物进行测序，结果显示在牙釉质型颅咽管瘤衍生的DNA样本中共有7/43处改变。观察到两个先前描述的β-连环蛋白突变，分别位于密码子33（TCT（Ser）>TGT（Cys））和密码子37（TCT（Ser）>TTT（Phe）），同时还观察到三个新的突变，分别位于密码子41（ACC（Thr）>ATC（Ile））、密码子33（TCT（Ser）>TAT（Tyr））和密码子32（GAC（Asp）>AAC（Asn））。在分析的22例垂体腺瘤和8例乳头型颅咽管瘤中均未出现任何序列改变。这些发现表明β-连环蛋白基因改变与牙釉质型颅咽管瘤之间存在关联。由于该基因产物参与发育，这些结果表明β-连环蛋白突变可能有助于先天性颅咽管瘤的起始和后续生长。
