Brain Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Brain Cancer, including details on symptoms, benign and malignant tumors, gliomas, treatment.

Molecular analysis of the EGFR gene in astrocytic gliomas: mRNA expression, quantitative-PCR analysis of non-homogeneous gene amplification and DNA sequence alterations.

Arjona D, Bello MJ, Alonso ME, Aminoso C, Isla A, De Campos JM, Sarasa JL, Gutierrez M, Villalobo A, Rey JA

Laboratorio de Oncogenética Molecular, Hospital Universitario La Paz, Paseo de la Castellana 261, Madrid, Spain.

The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with tyrosine kinase activity. This report investigates the presence of mutations, amplification and/or over-expression of the EGFR gene in 86 glial tumours including 44 glioblastomas, 21 anaplastic astrocytomas, and 21 WHO grade II astrocytomas, using polymerase chain reaction/single-strand conformation polymorphism, semiquantitative reverse-transcription-polymerase chain reaction (RT-PCR) and Southern Blot techniques. Gene amplification values were found in 34 tumours. Amplification levels were not uniform, as the transmembrane region presented lower amplification rates than extra- and intracellular domains. For the 19 samples with sufficient available tumour tissue we found over-expression in 11, and no EGFR mRNA expression in three. Ten cases showed deletion transcripts, and EGFR VIII was identified in all of these cases. One of the cases with EGFR vIII also presented a truncated form, C-958, while another showed an in frame tandem duplication of exons 18--25. We found 14 cases with sequence/structure gene alterations, including seven on which genomic novel DNA changes were identified: a missense mutation (1052C > T/Ala265Val), an insertion (InsCCC2498/Ins Pro748), three intronic changes (E6+72delG, E22--14C>G and E18--109T>C), a new polymorphic variant E12+ 22A > T, and one case that presented a 190 bp insertion, that was produced by the intron-7-exon-8 duplication and generated a truncated EGFR with intact exons 1--8 followed by an additional amino acidic sequence: Val-Ile-Met-Trp. These findings corroborate that EGFR is non-randomly involved in malignant glioma development and that different mutant forms participate in aberrant activation of tyrosine kinase pathways.

Published 12 July 2005 in Neuropathol Appl Neurobiol, 31(4): 384-94.
Full-text of this article is available online (may require subscription).

© 2004-2008 Brain Cancer Research Today. All Rights Reserved.