Cryns V L, Alexander J M, Klibanski A, Arnold A
Endocrine Unit, Massachusetts General Hospital, Boston.
J Clin Endocrinol Metab. 1993 Sep;77(3):644-6. doi: 10.1210/jcem.77.3.7690360.
Functional inactivation of the retinoblastoma (RB) tumor suppressor gene is important in the pathogenesis of many human tumors. Recently, the frequent occurrence of pituitary tumors was reported in mice genetically engineered to have one defective RB allele, a genetic background analogous to that of patients with familial retinoblastoma. The molecular pathogenesis of human pituitary tumors is largely unknown, and the potential role of RB gene inactivation in these neoplasms has not been examined. Consequently, we studied 20 human pituitary tumors (12 clinically nonfunctioning tumors, 4 somatotroph adenomas, 2 prolactinomas, and 2 corticotroph adenomas) for tumor-specific allelic loss of the RB gene using a highly informative polymorphic locus within the gene. Control leukocyte DNA samples from 18 of these 20 patients were heterozygous at this locus, permitting genetic evaluation of their paired tumor specimens. In contrast to the pituitary tumors in the mouse model, none of these 18 human tumors exhibited RB allelic loss. These findings indicate that RB gene inactivation probably does not play an important role in the pathogenesis of common types of human pituitary tumors.
视网膜母细胞瘤（RB）肿瘤抑制基因的功能失活在许多人类肿瘤的发病机制中具有重要意义。最近，据报道，在经过基因工程改造而具有一个缺陷RB等位基因的小鼠中频繁出现垂体肿瘤，这种遗传背景类似于家族性视网膜母细胞瘤患者。人类垂体肿瘤的分子发病机制在很大程度上尚不清楚，并且尚未研究RB基因失活在这些肿瘤中的潜在作用。因此，我们使用该基因内一个信息丰富的多态性位点，研究了20例人类垂体肿瘤（12例临床无功能肿瘤、4例生长激素腺瘤、2例催乳素瘤和2例促肾上腺皮质激素腺瘤）中RB基因的肿瘤特异性等位基因缺失情况。这20例患者中有18例的对照白细胞DNA样本在该位点是杂合的，从而能够对其配对的肿瘤标本进行遗传学评估。与小鼠模型中的垂体肿瘤不同，这18例人类肿瘤均未表现出RB等位基因缺失。这些发现表明，RB基因失活可能在常见类型的人类垂体肿瘤发病机制中不发挥重要作用。
