[Oncogene neu in spontaneous and induced rat schwannomas: a study using polymerase chain reaction]

Ethylnitrosourea (ENU) given transplacentally to rats induces schwannomas of the cranial, spinal and peripheral nerves with a high frequency of mutation in the neu proto-oncogene. To establish the requirement for such mutation in tumorigenesis of Schwann cells, spontaneous schwannomas from BD-VI strain rats were evaluated for transforming mutations in the transmembrane domain of the encoded protein for the neu proto-oncogene. Whereas all five schwannomas induced by ENU showed T/A transversions in codon 2012 of neu oncogene upon analysis by selective oligonucleotide hybridization and dideoxy sequencing of polymerize chain reaction amplified products from paraffin sections, only one of nine spontaneous schwannomas from untreated rats exhibited the same mutation. Examination of tumours for mutation in codon 12 of Ki-ras proto-oncogene revealed normal alleles. Our conclusions based on these data are that the high frequency of mutations in neu in ENU-induced tumours appears to be attributable to the carcinogen or to the period of development at which exposure occurred, and that transforming mutations of the transmembrane domain of neu, are not required for tumorigenesis of the Schwann cell.