P53 GENE-MUTATIONS IN PITUITARY-ADENOMAS - RARE EVENTS
P53 GENE-MUTATIONS IN PITUITARY-ADENOMAS - RARE EVENTS
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DOI：
10.1111/j.1365-2265.1994.tb02797.x
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发表时间：
1994-12-01
影响因子：
3.2
通讯作者：
LIGHTMAN, SL
中科院分区：
文献类型：
--
作者：
LEVY, A;HALL, L;LIGHTMAN, SL
在随机尸检中，隐匿性垂体腺瘤的发生率高达20%，但已知与垂体腺瘤相关的唯一癌基因gap仅在40%的生长激素瘤中发现，生长激素瘤是一种亚型，占垂体肿瘤的少数。p53肿瘤抑制基因的突变被认为与多达50%的人类癌症的发病机制有关，包括中枢神经系统肿瘤。本研究的目的是确定p53基因突变是否与pituitary adenomas.Design AND Patients垂体腺瘤组织片段从29例接受常规垂体切除术的垂体瘤包被在冷冻包埋介质和冷冻在-80 ° C在24小时内切除。其中生长激素腺瘤9例，促肾上腺皮质激素腺瘤4例，促乳腺激素腺瘤1例，内分泌功能不活跃腺瘤15例，均为非侵袭性临床表型。对连续的冷冻切片进行垂体前叶激素转录物的原位杂交分析，并进行组织学检查，以确保用于产生用于聚合酶链反应扩增的DNA模板的冷冻切片不被非肿瘤组织污染。和p53免疫阳性肿瘤中的外显子4-6，通过聚合酶链反应扩增并连接到载体pCR 2中。使用基于荧光的自动化系统（DuPont Genesis 2000）对来自人垂体腺瘤的含有克隆p53外显子的pCR 2的小规模质粒制备物的DHA进行测序，并与野生型序列进行比较。明显的突变被证实或反驳，通过测序进一步2-4克隆分离从同一template.RESULTS虽然野生型p53的免疫细胞化学染色模式显着不同的肿瘤之间，没有突变被确定在任何exonic sequence examined.CONCLUSIONS p53突变，至少在p53的高突变域，很少发生在人类垂体腺瘤。免疫细胞化学鉴定的p53蛋白的稳态水平增加可能是这些肿瘤中与其他细胞蛋白结合的结果。
OBJECTIVE Occult pituitary adenomas are said to occur in up to 20% of random autopsy examinations, yet the only oncogene known to be associated with pituitary adenomas, gap, is found in only 40% of somatotrophinomas, a subtype that accounts for a minority of pituitary tumours. Mutations of the p53 tumour suppressor gene are thought to be involved in the pathogenesis of as many as 50% of all human cancers, including tumours of the central nervous system. The objective of this study was to determine whether p53 gene mutations are associated with pituitary adenomas.DESIGN AND PATIENTS Fragments of pituitary adenoma tissue from 29 patients undergoing routine hypophysectomy for pituitary tumour were coated in cryostat embedding medium and frozen at -80 degrees C within 24 hours of resection. They consisted of 9 somatotroph, 4 corticotroph, 1 mammotroph and 15 endocrinologically inactive adenomas, all of the non-invasive clinical phenotype. Sequential frozen sections were subjected to in situ hybridization analysis for anterior pituitary hormone transcripts and examined histologically to ensure that the frozen sections used to generate DNA templates for polymerase chain reaction amplification were not contaminated with non-tumour tissue.MEASUREMENTS p53 exons 7 and 8, within which 98% of substitution mutations are thought to occur, and exons 4-6 in tumours immunopositive for p53, were amplified by polymerase chain reaction and ligated into the vector pCR2. DHA from small-scale plasmid preparations of pCR2 containing cloned p53 exons from human pituitary adenomas was sequenced using an automated fluorescence-based system (DuPont Genesis 2000) and compared with wild-type sequence. Apparent mutations were confirmed or refuted by sequencing a further 2-4 clones isolated from the same template.RESULTS Although immunocytochemical staining patterns for wild-type p53 varied markedly between different tumours, no mutations were identified in any of the exonic sequences examined.CONCLUSIONS p53 mutations, at least within the high mutation domains of p53, occur infrequently in human pituitary adenomas. Increased steady-state levels of p53 protein identified immunocytochemically may be a consequence of binding to other cellular proteins in these tumours.