The N-ras oncogene is activated in a human medulloblastoma cell line

Abstract

Medulloblastoma is a malignant brain tumor of early childhood whose cells resemble the primitive neuroepithelial cells found normally in the developing nervous system. Medulloblastoma may be caused by mutational events affecting primitive neuroepithelial cells and preventing their differentiation into postmitotic neurons. The human ras genes, H-ras, K-ras and N-ras, are members of a family of proto-oncogenes that are targets for mutational changes that convert these normal genes into active, transforming oncogenes. Here we report than the N-ras oncogene is activated in the human medulloblastoma cell line TE 671 by a mutation at the third position of codon 61. A point mutation at this location corresponds to a substitution of histidine for glutamine in the N-ras gene product, p21. The oncogenic activation was shown by focus-formation in NIH 3T3 cell transfection assays. The location of the mutation was established using oligonucleotide hybridization assays enhanced through in vitro amplification of N-ras coding sequences using the Taq polymerase chain reaction. N-ras activation may be one of the mutational events that subvert normal neuroectodermal differentiation and lead to medulloblastoma in children.