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International collaboration of neuroblastoma

神经母细胞瘤的国际合作

基本信息

批准号：
08042002
负责人：
HAYASHI Yasuhide
金额：
$ 3.84万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08042002/
关键词：
neuroblastoma N-myc gene p16 gene DCC gene DPC4 gene MADR2 gene p73 gene mass screening p16遺伝子 p15遺伝子疫抑制遺伝子マススクリーニング N-myc遺伝子

项目摘要

N-myc, p16, DCC, DPC4, MADR2 and p73 genes were analyzed in Japan, USA and Malaysia by Southern blotting, Northern blotting, Western blotting and PCR-single stand conformation polymorphism (SSCP). Loss of heterozygosity (LOH) in our Japanese study suggested high frequent LOH between D9S162 and IFNA on 9p, which included p16 gene. Homozygous deletion (HD) of p16 gene was not found in 81 Japanese samples (N-myc 6 samples). PCR-SSCP analysis identified only missense mutation, suggesting polymorphism. Absence or decreased expression of p16 gene was found in 6 of 10 Japanese cell lines and 6 of 9 USA cell lines, suggestings no significant difference between them. Hypermenthylation of the p16 gene was found in 6 of 10 Japanese cell lines and 6 of 9 USA cell lines, suggesting that hypermenthylation plays an important role for the development or progression of neuroblastoma. The commonly deleted region of 18q in neuroblastoma included DCC, DPC4 and MADR2 genes. Absence or reduced expression of DCC gene was found in half of the samples in 3 countries. PCR-SSCP analysis of DCC gene showed only missense mautation, suggesting polymorphism. Alterations of DPC4 and MDRR2 genes were relatively rare. These results suggested that DCC gene plays an important role in the dissemination of neuroblastoma, and that DPC4 and MAD2 gene are not involved in the development of neuroblastoma. Frequency of alterations of the p73 gene was not different among 3 countries. Our epidemiological study showed the frequency of the development of neuroblastoma increased (2 times) after mass screening. These results were found to be different from those in USA and Canada. Inetrnational Collaboration of neuroblastoma contributed to the pathogenesis of neuroblastoma in 3 countries.

采用Southern blotting、北方blotting、Western blotting和PCR-单链构象多态性（SSCP）技术对日本、美国和马来西亚的N-myc、p16、DCC、DPC 4、MADR 2和p73基因进行分析。在我们日本的研究中，杂合性丢失（洛）提示在D9 S162和IFNA之间在9 p上的高频率洛，其中包括p16基因。在81例日本人样本中未发现p16基因纯合性缺失（HD）（N-myc 6例）。PCR-SSCP分析仅发现错义突变，提示多态性。10株日本细胞系和9株美国细胞系中分别有6株和6株p16基因表达缺失或降低，两者之间无显著性差异。在10个日本细胞系中的6个和9个美国细胞系中的6个中发现p16基因的高薄荷基化，这表明高薄荷基化在神经母细胞瘤的发生或进展中起重要作用。在神经母细胞瘤中18 q基因缺失的区域包括DCC、DPC 4和MADR 2基因。在3个国家的样本中，有一半的样本DCC基因表达缺失或降低。PCR-SSCP分析DCC基因仅有错义突变，提示DCC基因多态性。DPC 4和MDRR 2基因的改变相对罕见。提示DCC基因在神经母细胞瘤的发生、发展中起重要作用，DPC 4和MAD 2基因与神经母细胞瘤的发生、发展无关。p73基因改变的频率在3个国家之间没有差异。我们的流行病学研究表明，在大规模筛查后，神经母细胞瘤的发生频率增加了2倍。这些结果与美国和加拿大的结果不同。神经母细胞瘤的国际协作促成了3个国家神经母细胞瘤的发病机制。