Gene dosage and mutational analyses of EGFR in oligodendrogliomas

  • Authors:
    • Carmen Franco-Hernandez
    • Victor Martinez-Glez
    • M. Eva Alonso
    • Jose M. De Campos
    • Alberto Isla
    • Jesus Vaquero
    • Manuel Gutierrez
    • Juan A. Rey
  • View Affiliations

  • Published online on: January 1, 2007     https://doi.org/10.3892/ijo.30.1.209
  • Pages: 209-215
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Abstract

We have studied amplification/gene-dosage and sequence variations of the EGFR gene in 41 oligodendroglial tumours graded according to the WHO classification (21 oligodendrogliomas grade II, 13 oligodendrogliomas grade III and 6 oligoastrocytomas grade II-III), using multiplex ligation-dependent probe amplification (MLPA), real-time quantitative PCR, and PCR/SSCP techniques. To determine gene-dose we studied exons 11 (extracellular domain) and 25 (intracellular domain) in the EGFR gene. Overdose (1- to 5-fold increase) was present in exon 11 in 21 of 41 samples (52.5% of cases) and in exon 25, in 7 of 41 samples (17.5% of cases). Gene amplification >5-fold increase) was present in exon 11, in 17 of 41 samples (42.5% of cases), and in exon 25 in 6 of 41 samples (15% of cases). Three tumours (two grade II oligodendrogliglioma, one mixed oligoastrocytoma) displayed high level amplifications: >100 gene copies were identified by both real-time quantitative PCR and MLPA analyses. Gene sequence alterations were identified by PCR/SSCP and sequencing in four cases: two missense mutations: G1051A (Ala351Thr) and G2216A (Arg739Hys); one nonsense mutation: C2934T (Asp978Asp); and an 18 bp deletion in position 2423-2441 of E19. These changes were present only in tumoral DNA, not in the corresponding constitutional patients' DNA. We also found four previously unidentified polymorphic variants: G2025A (Ala675Ala), C2233T (Leu745Leu), C2895T (Treo965Treo) and C3168T (Asp1056Asp), and three previously described polymorphic changes: E12+22 T↷A, G1748A (Arg583Lys) and A2547T (Glu849Glu). Our findings demonstrate that mutations and amplification/overdose in the EGFR gene are present in low-grade oligodendroglial tumours, and may contribute to the development of these brain neoplasms.

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January 2007
Volume 30 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Franco-Hernandez C, Martinez-Glez V, Alonso ME, De Campos JM, Isla A, Vaquero J, Gutierrez M and Rey JA: Gene dosage and mutational analyses of EGFR in oligodendrogliomas. Int J Oncol 30: 209-215, 2007
APA
Franco-Hernandez, C., Martinez-Glez, V., Alonso, M.E., De Campos, J.M., Isla, A., Vaquero, J. ... Rey, J.A. (2007). Gene dosage and mutational analyses of EGFR in oligodendrogliomas. International Journal of Oncology, 30, 209-215. https://doi.org/10.3892/ijo.30.1.209
MLA
Franco-Hernandez, C., Martinez-Glez, V., Alonso, M. E., De Campos, J. M., Isla, A., Vaquero, J., Gutierrez, M., Rey, J. A."Gene dosage and mutational analyses of EGFR in oligodendrogliomas". International Journal of Oncology 30.1 (2007): 209-215.
Chicago
Franco-Hernandez, C., Martinez-Glez, V., Alonso, M. E., De Campos, J. M., Isla, A., Vaquero, J., Gutierrez, M., Rey, J. A."Gene dosage and mutational analyses of EGFR in oligodendrogliomas". International Journal of Oncology 30, no. 1 (2007): 209-215. https://doi.org/10.3892/ijo.30.1.209