Analysis of p53 tumor suppressor gene and MDM2 gene in solid tumors in childhood.

儿童实体瘤p53抑癌基因和MDM2基因分析

• 批准号: 05671495
• 负责人: TAKAHASHI Hiroshi
• 金额: $ 1.34万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671495/
• 关键词: neuroblastoma; tumor suppressor gene; p53; oncogene; ras; 癌抑制遺伝子; p53遺伝子; 神経芽細胞腫; DNA突然変異

The p53 gene frequently is affected by point mutations or deletions that contribute to the onset and progression of a wide variety of human adult solid tumors. Neuroblastoma is a common childhood malignancy of the sympathetic nervous system. However, to our knowledge, this gene alteration has been little analyzed in neuroblastoma.In this project, we prepared genomic DNA samples which were extracted from paraffin embedded blocks of 36 primary neuroblastomas. We screened for the presence of mutations in exons 5-8 of the p53 gene where over 90% of mutations have been reported to be located in human cancer. We also examined mutations of the K-ras and N-ras gene which are involved in a number of neoplasms. The screening technique employed polymerase chain reaction / single-strand conformation polymorphism analysis (PCR-SSCP) and potential mutations were further confirmed by a sequence analysis.In consequence, no mutations were detected within the exon 5-8 of the p53 gene and exon 1-2 of the K-ras and N-ras gene, regardless of the age, sex clinical staging and histological classification. Our data suggests that p53 and ras mutations do not contribute to the etiology of neuroblastomas, but other genes presumably play a major role in this tumor.Note ; Analysis of MDM2 gene amplification was so difficult due to severe fragmentation of DNA that we could not accomplish it.

p53 基因经常受到点突变或缺失的影响，从而导致多种成人实体瘤的发生和进展。神经母细胞瘤是一种常见的儿童交感神经系统恶性肿瘤。然而，据我们所知，神经母细胞瘤中的这种基因改变很少被分析。在这个项目中，我们准备了从 36 个原发性神经母细胞瘤的石蜡包埋块中提取的基因组 DNA 样本。我们筛选了 p53 基因外显子 5-8 中是否存在突变，据报道，超过 90% 的突变位于人类癌症中。我们还检查了与许多肿瘤有关的 K-ras 和 N-ras 基因的突变。筛查技术采用聚合酶链反应/单链构象多态性分析（PCR-SSCP），并通过序列分析进一步确认潜在突变。因此，无论年龄、性别、临床分期和组织学分类，p53基因的外显子5-8以及K-ras和N-ras基因的外显子1-2内均未检测到突变。我们的数据表明，p53 和 ras 突变不会导致神经母细胞瘤的病因，但其他基因可能在该肿瘤中发挥主要作用。由于 DNA 严重断裂，MDM2 基因扩增分析非常困难，我们无法完成。

项目成果

木藤克己,他: "神経芽腫におけるp53遺伝子及びK-ras,N-ras遺伝子の点突然変異の検討" 小児がん. 29. 295-297 (1992)

Katsumi Kito 等人：“神经母细胞瘤中 p53 基因以及 K-ras 和 N-ras 基因点突变的检查”《小儿癌症》29. 295-297 (1992)。

高橋広,他: "愛媛県における"神経芽細胞腫"マス・スクリーニングの現状とその治療成績" 愛媛医学. 9. 748-745 (1990)

Hiroshi Takahashi 等：“爱媛县神经母细胞瘤大规模筛查的现状及其治疗结果”爱媛医疗。 9. 748-745 (1990)

高橋 広,他: "愛媛県における"神経芽細胞腫"マス・スクリーニングの現状とその治療成績" 愛媛医学. 9. 748-745 (1990)

Hiroshi Takahashi 等：“爱媛县神经母细胞瘤大规模筛查的现状及其治疗结果”爱媛医疗。 9. 748-745 (1990)

Takahashi, H., Kubota, M., Kimura, S.et al.: "Mass screening for neuroblastoma in Ehime prefecture." Ehime Medical journal. 9. 748-745 (1990)

Takahashi, H.、Kubota, M.、Kimura, S.等人：“爱媛县神经母细胞瘤的大规模筛查。”

Kito, K., Kimura, S.et al.: "Absence of K-ras, Ha-ras and p53 gene mutations in neuroblastoma." Jpn.J.Pediatr.Oncol.29. 295-297 (1992)

Kito, K.、Kimura, S.等人：“神经母细胞瘤中不存在 K-ras、Ha-ras 和 p53 基因突变。”