neu mutations and loss of normal allele in schwannomas induced by N-ethyl-N-nitrosourea in rats.
The mutational activation of the neu proto-oncogene was analyzed in schwannomas of the peripheral nervous system transplacentally induced by N-ethyl-N-nitrosourea (ENU) in rats. All nine primary schwannomas investigated contained a T-->A transversion mutation at nucleotide 2012 of the neu gene, leading to the substitution of valine to glutamic acid in the transmembrane domain. Loss of the wild-type allele occurred in five of nine (56%) primary schwannomas. All four ENU-induced schwannomas transplanted in syngenic hosts (2-14 passages) showed the T-->A transversion mutation and loss of the wild-type allele. These data suggest that mutation of one allele together with loss of the wild-type allele constitutes two critical steps in the progression of rat schwannomas. Since c-erbB-2, the human counterpart of the rat neu gene is frequently involved by amplification in the development of human gastric cancer [30], we screened 12 rat gastric carcinomas induced by N-methyl-N-nitrosourea (MNU) for mutations in the neu gene. However, none of these tumors contained mutations.
Ohgaki
H
H
Institute of Neuropathology, University Hospital CH-8091 Zürich, Switzerland.
Vogeley
K T
KT
Kleihues
P
P
Wechsler
W
W
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D005038:Ethylnitrosourea; D005260:Female; D017353:Gene Deletion; D008969:Molecular Sequence Data; D009442:Neurilemmoma / Q000139:chemically induced / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D017422:Sequence Analysis, DNA
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D005038:Ethylnitrosourea