Herman V, Drazin N Z, Gonsky R, Melmed S
Department of Medicine, Cedars-Sinai Medical Center-UCLA School of Medicine 90048.
J Clin Endocrinol Metab. 1993 Jul;77(1):50-5. doi: 10.1210/jcem.77.1.8100831.
Although pituitary tumors arise as benign monoclonal neoplasms, genetic alterations have not readily been identified in these adenomas. We studied restriction fragment abnormalities involving the GH gene locus, and mutations in the p53 and H-, K- and N-ras genes in 22 human GH cell adenomas. Twenty two nonsecretory adenomas were also examined for p53 and ras gene mutations. Seven prolactinoma DNA samples were tested for deletions in the multiple endocrine neoplasia-1 (MEN-1) locus, as well as for rearrangements in the hst gene, a member of the fibroblast growth factor family. Pituitary adenoma tissue and lymphocytes were obtained from patients at the time of transsphenoidal surgery. In DNA from GH-cell adenomas, identical GH restriction patterns were detected in both pituitary and lymphocyte DNA in all patients and in one patient with a mixed GH-TSH cell adenoma. Using polymerase chain reaction (PCR)-single stranded conformation polymorphism analysis, no mutations were detected in exons 5, 6, 7, and 8 of the p53 gene in GH cell adenomas nor in 22 nonsecretory adenomas. Codons 12/13 and 61 of H-ras, K-ras, and N-ras genes were also intact in GH cell adenomas and in nonsecretory adenomas. Site-specific probes for chromosome 11q13 including PYGM, D11S146, and INT2 were used in 7 sporadic PRL-secreting adenomas to detect deletions of the MEN-1 locus on chromosome 11. One patient was identified with a loss of 11p, and the remaining 6 patients did not demonstrate loss of heterozygosity in the pituitary 11q13 locus, compared to lymphocyte DNA. None of these patients, demonstrated hst gene rearrangements which also maps to this locus. These results show that p53 and ras gene mutations are not common events in the pathogenesis of acromegaly and nonsecretory tumors. Although hst gene rearrangements and deletions of 11q13 are not associated with sporadic PRL-cell adenoma formation, a single patient was detected with a partial loss of chromosome 11, including the putative MEN-1 site.
虽然垂体瘤以良性单克隆肿瘤形式出现，但在这些腺瘤中尚未轻易鉴定出基因改变。我们研究了22例人类生长激素（GH）细胞腺瘤中涉及GH基因座的限制性片段异常以及p53和H -、K -、N - ras基因的突变。还对22例无分泌功能的腺瘤进行了p53和ras基因突变检测。检测了7份催乳素瘤DNA样本中多内分泌腺瘤1型（MEN - 1）基因座的缺失以及成纤维细胞生长因子家族成员hst基因的重排。垂体腺瘤组织和淋巴细胞在经蝶窦手术时取自患者。在GH细胞腺瘤的DNA中，所有患者以及1例混合性GH - TSH细胞腺瘤患者的垂体和淋巴细胞DNA中均检测到相同的GH限制性图谱。使用聚合酶链反应（PCR）-单链构象多态性分析，在GH细胞腺瘤和22例无分泌功能的腺瘤的p53基因外显子5、6、7和8中均未检测到突变。GH细胞腺瘤和无分泌功能的腺瘤中H - ras、K - ras和N - ras基因的第12/13密码子和第61密码子也均完整。在7例散发性分泌催乳素的腺瘤中使用了针对11q13染色体的位点特异性探针，包括PYGM、D11S146和INT2，以检测11号染色体上MEN - 1基因座的缺失。1例患者被鉴定为11p缺失，与淋巴细胞DNA相比，其余6例患者在垂体11q13基因座未显示杂合性缺失。这些患者均未显示出也定位于该基因座的hst基因重排。这些结果表明，p53和ras基因突变在肢端肥大症和无分泌功能肿瘤的发病机制中并非常见事件。虽然hst基因重排和11q13缺失与散发性催乳素细胞腺瘤的形成无关，但检测到1例患者染色体11部分缺失，包括假定的MEN - 1位点。
