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Neuroblastoma with DNA Amplification and Rearrangement in the N-myc Gene Region¹

Department of General Medicine, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima 734 [E. H., T. Y.], and Department of Genetics, Radiation Effects Research Foundation, Hiroshima [K. H.], Japan

We detected a rearrangement in the N-myc gene region in a neuroblastoma from a 9-month-old girl. In this case, the N-myc gene was amplified 50-fold in the primary tumor, the lymph node metastasis, and the hepatic metastasis. The rearrangement was detected only in the primary tumor and the lymph node metastasis, whereas N-myc RNA and protein expression were detected only in the primary tumor and the hepatic metastasis. Both the rearranged N-myc gene and the normal N-myc gene were amplified 25-fold, and the rearrangement occurred 723 nucleotides downstream from the 3' end of exon 3. The cell line (NH-6) derived from the primary tumor showed N-myc gene amplification without this rearrangement. These results suggest the following: (a) the primary tumor had at least two clones; (b) the rearrangement interrupted N-myc gene expression; and (c) oncogenesis preceded N-myc gene amplification.

¹ This work was supported by Grant-in-Aid 1-29 for Cancer Research from the Ministry of Health and Welfare, Japan.

² To whom requests for reprints should be addressed.

Received 3/12/90. Accepted 1/21/91.

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