Analysis genetic changes in human endocrine tumors

分析人类内分泌肿瘤的遗传变化

• 批准号: 04671484
• 负责人: YOSHIMOTO Katsuhiko
• 金额: $ 1.41万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671484/
• 关键词: endocrine tumors; mutation; ras gene; p53 gene; Gsalpha gene; 多発性内分泌腫瘍症1型; 第11染色体; 塩基置換; PCR-SSCP

To elucidate the molecular basis for endocrine tumorigenesis, ras, p53, and Gsalpha mutations in human endocrine tumors were analyzed.1. ras mutationsMutations of the H-, K-, N-ras genes were examined from 171 tumors by polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP). Four out of 24 thyroid follicular adenomas contained mutated N-ras codon 61, and one contained the mutated H-ras codon 61. One of the 19 pheochromocyttomas revealed mutation of the H-ras codon 13. One of the 2 pituitary carcinomas contained mutation of the H-ras codon 12.2. p53 mutationsExons 5 through 10 of the p53 gene were studied from 134 tumors and 6 human endocrine cancer-derived cell lines by PCR-SSCP.Mutations were detected in 4 tumors, including one parathyroid adenomas and 3 throid carcinoma cell lines. In all of 3 tumor cell lines, the normal allele including the p53 gene was lost.3. Gsalpha mutationsMutation at codons 201 or 227 of the Gsalpha gene were screened from 197 tumors by PCR-primer-introduced restriction analysis(PIRA). The Gsalpha mutations were present in 4 of 43 GH-secreting pituitary adenomas, 4 of 30 papillary thyroid carcinomas, and 1 of 19 adrenocortical adenomas.Conclusion : Mutation of the ras, p53, and Gsalpha genes may not involved in the pathogenesis of a large population of human endocine tumors.

为了阐明内分泌肿瘤发生的分子基础，我们分析了人类内分泌肿瘤中ras、p53和Gsalpha突变.应用聚合酶链反应-单链构象多态性（PCR-SSCP）技术检测了171例肿瘤组织中H-、K-、N-ras基因的突变。24例甲状腺滤泡性腺瘤中有4例含有突变的N-ras密码子61，1例含有突变的H-ras密码子61。19例嗜铬细胞瘤中有1例H-ras基因第13密码子突变。2例垂体癌中1例H-ras基因第12.2位密码子突变。应用PCR-SSCP技术对134例肿瘤和6株人内分泌癌细胞系的p53基因外显子5 ~ 10进行了研究，发现4例肿瘤（包括1例甲状旁腺腺瘤和3例甲状腺癌细胞系）存在p53基因外显子5 ~ 10的突变。3种肿瘤细胞系中，包括p53基因在内的正常等位基因均丢失. Gsalpha基因突变采用PCR-引物引入限制性内切酶分析（PIRA）方法，从197例肿瘤中筛选出Gsalpha基因第201或227位密码子突变。43例垂体GH腺瘤中4例、30例甲状腺乳头状癌中4例、19例肾上腺皮质腺瘤中1例存在Gsalpha突变。结论：ras、p53和Gsalpha基因突变可能不参与大量人类endocine肿瘤的发病。

项目成果

Katsuhiko Yoshimoto et al.: "Role of p53 mutartions in endocrine tumorigenesis : Mutation detection by polymerase chain reaction-single strand conformation polymorphism" Cancer Res. 52. 5061-5064 (1992)

Katsuhiko Yoshimoto 等人：“p53 突变在内分泌肿瘤发生中的作用：聚合酶链反应-单链构象多态性检测突变”Cancer Res。

Yoshimoto K et al.: "Critical commentary to MEN I with mediastinal carcinoid" Pathology Res.and Proct.189. 1097-1099 (1993)

Yoshimoto K 等人：“对纵隔类癌 MEN I 的批判性评论”Pathology Res.and Proct.189。

Yoshimoto K et al.: "ras mutation in endocrine tumors:mutation detection by polymerase chain reaction-single strand conformation polymorphism" Jpn J Cancer Res. 83. 1057-1062 (1992)

Yoshimoto K等：“内分泌肿瘤中的ras突变：聚合酶链反应-单链构象多态性检测突变”Jpn J Cancer Res。

Yoshimoto K et al.: "Rare mutations of the Gs alpha subunitgeus in human endocrine tumors:mutation detection by polymerase chain reaction-primer-introduced restriction analysis." Cancer. 72. 1386-1393 (1993)

Yoshimoto K 等人：“人类内分泌肿瘤中 Gs α 亚基的罕见突变：通过聚合酶链反应-引物引入的限制性分析检测突变。”

Katsuhiko Yoshimoto et al.: "ras mutartions in endocrine tumors : Mutation detection by polymerase chain reaction-single strand conformation polymorphism" Jpn J Cancer Res. 83. 1057-1062 (1992)

Katsuhiko Yoshimoto 等：“内分泌肿瘤中的 ras 突变：聚合酶链反应-单链构象多态性检测突变”Jpn J Cancer Res。