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Infrequent transforming mutations in the transmembrane domain of the neu oncogene in spontaneous rat schwannomas

✍ Scribed by Alan O. Perantoni; Vladimir S. Turusov; Gregory S. Buzard; Jerry M. Rice

Publisher
John Wiley and Sons
Year
1994
Tongue
English
Weight
588 KB
Volume
9
Category
Article
ISSN
0899-1987

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✦ Synopsis

Abstract

Ethylnitrosourea (ENU) given transplacentally to rats induces schwannomas of the cranial, spinal, and peripheral nerves, with a high frequency of mutations in the neu proto‐oncogene. To establish the requirement for such mutations in tumorigenesis of the Schwann cell, spontaneous schwannomas from BD‐VI rats were evaluated for transforming mutations in the transmembrane domain of the protein encoded by the neu protooncogene. While all five schwannomas induced transplacentally with ENU were shown to contain T←A transversions in base 2012 of neu by selective oligonucleotide hybridization and dideoxy sequencing of polymerase chain reaction–amplified products from paraffin sections, only one of nine spontaneous schwannomas from untreated rats had the same mutation. Examination of tumors for mutations in codon 12 of Ki‐ras revealed normal alleles. Therefore, the high frequency of mutations in neu in ENU‐induced tumors may be directly attributable to the carcinogen or to the period of development at which exposure occurred, and transforming mutations of the transmembrane domain of neu are not required for tumorigenesis of the Schwann cell. © 1994 Wiley‐Liss, Inc.

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