neu mutations and loss of normal allele in schwannomas induced by N-ethyl-N-nitrosourea in rats.

Abstract:

: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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Ohgaki H,Vogeley KT,Kleihues P,Wechsler W

doi

10.1016/0304-3835(93)90073-i

subject

Has Abstract

pub_date

1993-06-15 00:00:00

pages

45-50

issue

1-2

eissn

0304-3835

issn

1872-7980

pii

0304-3835(93)90073-I

journal_volume

70

pub_type

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