Monoclonality of corticotroph macroadenomas in Cushing's disease.
Monoclonality of corticotroph macroadenomas in Cushing's disease.
复制标题
库欣病中促肾上腺皮质激素大腺瘤的单克隆性。
DOI：
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发表时间：
1992
影响因子：
5.8
通讯作者：
X. Bertagna
中科院分区：
文献类型：
--
作者：
C. Gicquel;Y. Bouc;J. Luton;F. Girard;X. Bertagna
库欣病垂体ACTH过度分泌的病理生理机制尚不清楚。促肾上腺皮质激素细胞的聚集是垂体的原发性事件还是由下丘脑促肾上腺皮质激素释放因子的产生增加引起的，这个问题仍有争议。确定此类垂体病变是否具有克隆性具有重要的概念和实践意义。通过使用DNA探针M27 β的X染色体失活分析确定促肾上腺皮质激素细胞腺瘤的克隆组成，所述DNA探针M27 β在90%的女性中检测到多等位基因多态性。通过Pst I的第一消化揭示了多态性。通过MspI或其甲基化敏感的异构体HpaII的第二次消化，区分活性拷贝和非活性拷贝。从11例引起库欣病或纳尔逊综合征的促肾上腺皮质激素细胞大腺瘤中提取DNA。11例女性患者中有8例为该基因座杂合子，并被纳入研究。5只雌性动物的血液白细胞可用，并用作对照。所有8个肿瘤显示单克隆模式，而5个白细胞DNA是多克隆的。我们的研究结果表明，体细胞修饰在促肾上腺皮质激素细胞大腺瘤的发病机制中起着重要作用，允许遗传异常细胞的单克隆扩增。
The pathophysiological mechanism of pituitary ACTH oversecretion in Cushing's disease remains unclear. The question of whether a collection of corticotroph cells is a primary pituitary event or is driven by increased production of hypothalamic corticotropin releasing factor is still debated. Establishing whether or not there is a clonal nature of such pituitary lesions has important conceptual and practical implications. Clonal composition of corticotroph cell adenomas was determined by X chromosome inactivation analysis using a DNA probe, M27 beta, which detects a multiallelic polymorphism in 90% of females. A first digestion by PstI reveals the polymorphism. A second digestion by MspI or its methylation sensitive isoschizomer HpaII, distinguishes the active from the inactive copy. DNA was extracted from 11 corticotroph macroadenomas responsible for Cushing's disease or Nelson's syndrome. Eight of the 11 female patients were heterozygous for the locus and included in the study. Blood leukocytes were available for 5 females and were used as controls. All 8 tumors demonstrated a monoclonal pattern while the 5 leukocyte DNA were polyclonal. Ours results show that a somatic modification plays an important role in the pathogenesis of corticotroph macroadenomas allowing monoclonal expansion of a genetically aberrant cell.
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影响因子：
158.5
作者：
ARNOLD, A;STAUNTON, CE;KRONENBERG, HM
通讯作者：
KRONENBERG, HM
影响因子：
11.2
作者：
B. Vogelstein;E. Fearon;S. Hamilton;A. C. Preisinger;H. Willard;A. Michelson;A. Riggs;S. Orkin
通讯作者：
B. Vogelstein;E. Fearon;S. Hamilton;A. C. Preisinger;H. Willard;A. Michelson;A. Riggs;S. Orkin
影响因子：
15.9
作者：
ALEXANDER, JM;BILLER, BMK;KLIBANSKI, A
通讯作者：
KLIBANSKI, A
影响因子：
56.9
作者：
FEARON, ER;HAMILTON, SR;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
56.9
作者：
VOGELSTEIN, B;FEARON, ER;FEINBERG, AP
通讯作者：
FEINBERG, AP