Neuroblastoma Transfection and Transformation

Gilbert, Fred

Abstract

Transformation of the mouse line NIH 3T3 following transfection with DNAs from human neuroblastomas (Nbs) was shown to be associated with a change in membrane glycoproteins. When compared with nontransformed 3T3, cell membranes from 3T3 transformants contained larger amounts of more highly branched glycoproteins. A novel glycoprotein change previously described in neuroectodermal tumors, fucosyl residues in an unusual linkage, was not found in these transformants, suggesting that this particular alteration represents a later event in the oncogenic cascade. In a review of karyotypes from 35 Nbs, only chromosomes 1 and 17 were found to be involved in structural or numerical aberrations in greater than 20% of cases. Two other cytogenetic abnormalities, homogeneously staining regions (HSR) and double minutes (DMS), were also noted in twothirds of the cases. We postulate that the particular chromosome abnormalities associated with a loss of genetic information in Nb (deletions of chromosome 1p) point to the location of gene(s) responsible for tumorigenesis; those changes associated with the addition of genetic information to the cell (extra 1q, 17q, and HSR/DMS), are likely to contribute to tumor progression. The latter is supported by our demonstration of extra 1q material in tumor samples obtained over time from the same patient, and from an increase in length of an HSR associated with enhanced tumorigenicity in a nude mouse tumor model. We have also shown that the genes amplified in the HSR/DMS of different Nbs all bear homology to the v-myc oncogene (either as c-myc or N-myc). Studies to define the mechanism(s) of gene amplification in Nb are in progress. (M)