Molecular Genetics of Pediatric Brain Stem Gliomas. Application of PCR Techniques to Small and Archival Brain Tumor Specimens

Abstract

Brainstem gliomas are pediatricastrocytomas that histologically resemble adult supratentorial astrocytomas such as glioblastomas multiforme(GBM). Our molecular genetic studieshave suggested that adult GBMcan be divided into two geneticsubsets: tumors with p53 tumor suppressor gene mutationsand chromosome 17p loss that occur more commonlyin youngerpatients; and tumors with epidermalgrowth factor receptor(EGFR)gene amplification that occur more commonly in older patients. Brain stem gliomas have not been studied sincebiopsiesof these tumors are rare and extremely small.We investigated the moleculargenetic composition of seven brain stem glioblastomas (two small biopsies, five autopsies) using polymerase chain reaction(PCR) assaysforchromosomal loss, genemutation and gene amplification. Fourcaseslost portions of chromosome 17p that included the p53 gene. These four cases and one additional case had mutations in the p53 gene. None of the cases showed amplification of the EGFR gene. Allelic losses of the longarm of chromosome 10 were noted in four cases. These resultssuggest similaritiesbetween pediatricbrainstem glioblastomas and thoseGBM that occurin younger adult patients, and confirm the utility of PCR-based means of studying small and archival brain tumor specimens.