ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma

Richard J. Gilbertson, D. Ashley Hill, Roberto Hernan, Mehmet Kocak, Russell Geyer, Jim Olson, Amar Gajjar, Lisa Rush, Ronald L. Hamilton, Sydney D. Finkelstein, Ian F. Pollack

Research output: Contribution to journalArticle

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Abstract

Purpose: This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades II-IV) pediatric brain stem glioma (BSG) and determine the relationship of these abnormalities to expression and mutation of TP53 and tumor grade. Experimental Design: After central pathology review, the incidence of ERBB1 amplification and overexpression was determined in 28 samples (18 surgical biopsy and 10 postmortem specimens) of BSG using quantitative PCR and immunohistochemistry, respectively. Mutation and expression of TP53 were also determined in these same samples by direct sequence analysis of microdissected tumor material and immunohistochemistry, respectively. All experimental procedures were performed blind to tumor grade. Results: Twelve, 9, and 7 tumors were classified as WHO grades II, III, and IV, respectively. A significant increase in ERBB1 expression was observed with increasing tumor grade (P < 0.001). Two grade IV tumors displayed intense membranous ERBB1 expression in 90% of tumor cells in association with high-level ERBB1 gene amplification. One grade III tumor also contained low-level amplification of ERBB1. Six tumors demonstrated TP53 nuclear immunoreactivity, and six contained a mutation in TP53. No correlation was observed between abnormalities in TP53 and either tumor grade or amplification and overexpression of ERBB1. Conclusions: These data suggest that ERBB1 signaling is important for the development of childhood BSG and is worthy of study as a therapeutic target in this disease. Our data also indicate that the genetics of childhood BSG are complex and include both grade-dependent amplification and overexpression of ERBB1 and grade-independent expression and mutation of TP53.

Original languageEnglish (US)
Pages (from-to)3620-3624
Number of pages5
JournalClinical Cancer Research
Volume9
Issue number10 I
StatePublished - Oct 1 2003

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Glioma
Brain Stem
Pediatrics
Neoplasms
Mutation
Immunohistochemistry
Gene Amplification
Incidence
Sequence Analysis
Research Design
Pathology
Biopsy
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Gilbertson, R. J., Hill, D. A., Hernan, R., Kocak, M., Geyer, R., Olson, J., ... Pollack, I. F. (2003). ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. Clinical Cancer Research, 9(10 I), 3620-3624.

ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. / Gilbertson, Richard J.; Hill, D. Ashley; Hernan, Roberto; Kocak, Mehmet; Geyer, Russell; Olson, Jim; Gajjar, Amar; Rush, Lisa; Hamilton, Ronald L.; Finkelstein, Sydney D.; Pollack, Ian F.

In: Clinical Cancer Research, Vol. 9, No. 10 I, 01.10.2003, p. 3620-3624.

Research output: Contribution to journalArticle

Gilbertson, RJ, Hill, DA, Hernan, R, Kocak, M, Geyer, R, Olson, J, Gajjar, A, Rush, L, Hamilton, RL, Finkelstein, SD & Pollack, IF 2003, 'ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma', Clinical Cancer Research, vol. 9, no. 10 I, pp. 3620-3624.
Gilbertson RJ, Hill DA, Hernan R, Kocak M, Geyer R, Olson J et al. ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. Clinical Cancer Research. 2003 Oct 1;9(10 I):3620-3624.
Gilbertson, Richard J. ; Hill, D. Ashley ; Hernan, Roberto ; Kocak, Mehmet ; Geyer, Russell ; Olson, Jim ; Gajjar, Amar ; Rush, Lisa ; Hamilton, Ronald L. ; Finkelstein, Sydney D. ; Pollack, Ian F. / ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 10 I. pp. 3620-3624.
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abstract = "Purpose: This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades II-IV) pediatric brain stem glioma (BSG) and determine the relationship of these abnormalities to expression and mutation of TP53 and tumor grade. Experimental Design: After central pathology review, the incidence of ERBB1 amplification and overexpression was determined in 28 samples (18 surgical biopsy and 10 postmortem specimens) of BSG using quantitative PCR and immunohistochemistry, respectively. Mutation and expression of TP53 were also determined in these same samples by direct sequence analysis of microdissected tumor material and immunohistochemistry, respectively. All experimental procedures were performed blind to tumor grade. Results: Twelve, 9, and 7 tumors were classified as WHO grades II, III, and IV, respectively. A significant increase in ERBB1 expression was observed with increasing tumor grade (P < 0.001). Two grade IV tumors displayed intense membranous ERBB1 expression in 90{\%} of tumor cells in association with high-level ERBB1 gene amplification. One grade III tumor also contained low-level amplification of ERBB1. Six tumors demonstrated TP53 nuclear immunoreactivity, and six contained a mutation in TP53. No correlation was observed between abnormalities in TP53 and either tumor grade or amplification and overexpression of ERBB1. Conclusions: These data suggest that ERBB1 signaling is important for the development of childhood BSG and is worthy of study as a therapeutic target in this disease. Our data also indicate that the genetics of childhood BSG are complex and include both grade-dependent amplification and overexpression of ERBB1 and grade-independent expression and mutation of TP53.",
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AU - Hernan, Roberto

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AU - Geyer, Russell

AU - Olson, Jim

AU - Gajjar, Amar

AU - Rush, Lisa

AU - Hamilton, Ronald L.

AU - Finkelstein, Sydney D.

AU - Pollack, Ian F.

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N2 - Purpose: This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades II-IV) pediatric brain stem glioma (BSG) and determine the relationship of these abnormalities to expression and mutation of TP53 and tumor grade. Experimental Design: After central pathology review, the incidence of ERBB1 amplification and overexpression was determined in 28 samples (18 surgical biopsy and 10 postmortem specimens) of BSG using quantitative PCR and immunohistochemistry, respectively. Mutation and expression of TP53 were also determined in these same samples by direct sequence analysis of microdissected tumor material and immunohistochemistry, respectively. All experimental procedures were performed blind to tumor grade. Results: Twelve, 9, and 7 tumors were classified as WHO grades II, III, and IV, respectively. A significant increase in ERBB1 expression was observed with increasing tumor grade (P < 0.001). Two grade IV tumors displayed intense membranous ERBB1 expression in 90% of tumor cells in association with high-level ERBB1 gene amplification. One grade III tumor also contained low-level amplification of ERBB1. Six tumors demonstrated TP53 nuclear immunoreactivity, and six contained a mutation in TP53. No correlation was observed between abnormalities in TP53 and either tumor grade or amplification and overexpression of ERBB1. Conclusions: These data suggest that ERBB1 signaling is important for the development of childhood BSG and is worthy of study as a therapeutic target in this disease. Our data also indicate that the genetics of childhood BSG are complex and include both grade-dependent amplification and overexpression of ERBB1 and grade-independent expression and mutation of TP53.

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