International collaboration of neuroblastoma

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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.