Yoshimoto K, Tanaka C, Yamada S, Kimura T, Iwahana H, Sano T, Itakura M
Otsuka Department of Clinical and Molecular Nutrition, The University of Tokushima, Kuramoto-cho, Japan.
Eur J Endocrinol. 1997 Jan;136(1):74-80. doi: 10.1530/eje.0.1360074.
The p16INK4A and p15INK4B genes on chromosome 9p21 encode the p16 and p15 inhibitors of cyclin D/cyclin-dependent kinase 4 complexes respectively. Mutations and deletions of the p16INK4A gene have been found in melanomas and many other types of tumors. To assess the role of the p16INK4A and p15NK4B genes in tumorigenesis of the pituitary gland, 31 sporadic pituitary adenomas and 2 pituitary adenomas in familial acrogigantism were examined for loss of heterozygosity on 9p21-22 and screened for mutations in the p161NK4A and p15INK4B genes. To identify pituitary adenomas which had lost 9p21-22, pituitary adenomas were genotyped with markers flanking the p16INK4A and p15INK4B loci. The frequency of mutations in coding regions of the p16INK4A and the p15INK4B genes in pituitary adenomas was determined with polymerase chain reaction-single strand conformation polymorphism analysis and sequencing of variants. Of the 33 pituitary adenomas, two revealed loss of 9p21-22 sequences, but none of them had tumor-specific mutations. We conclude that mutations of the p16INK4A and p15INK4B genes are not required for tumorigenesis of the pituitary gland.
位于9号染色体p21区域的p16INK4A和p15INK4B基因分别编码细胞周期蛋白D/细胞周期蛋白依赖性激酶4复合物的p16和p15抑制剂。在黑色素瘤和许多其他类型的肿瘤中已发现p16INK4A基因的突变和缺失。为了评估p16INK4A和p15NK4B基因在垂体肿瘤发生中的作用，对31例散发性垂体腺瘤和2例家族性肢端肥大症中的垂体腺瘤进行了9p21 - 22杂合性缺失检测，并筛查了p161NK4A和p15INK4B基因的突变。为了鉴定丢失9p21 - 22的垂体腺瘤，使用位于p16INK4A和p15INK4B基因座侧翼的标记对垂体腺瘤进行基因分型。通过聚合酶链反应 - 单链构象多态性分析和变异体测序确定垂体腺瘤中p16INK4A和p15INK4B基因编码区的突变频率。在33例垂体腺瘤中，有2例显示9p21 - 22序列缺失，但均无肿瘤特异性突变。我们得出结论，垂体肿瘤发生不需要p16INK4A和p15INK4B基因的突变。
