Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel.

Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Research Abstract Details 

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Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Abstract Text:

Jann N Sarkaria,Lin Yang,Patrick T Grogan,Gaspar J Kitange,Brett L Carlson,Mark A Schroeder,Evanthia Galanis,Caterina Giannini,Wenting Wu,Eduard B Dinca,C David James,

In the current study, we examined a panel of serially passaged glioblastoma xenografts, in the context of an intracranial tumor therapy response model, to identify associations between glioblastoma molecular characteristics and tumor sensitivity to the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib. From an initial evaluation of 11 distinct glioblastoma xenografts, two erlotinib-sensitive tumors were identified, each having amplified EGFR and expressing wild-type PTEN. One of these tumors expressed truncated EGFRvIII, whereas the other expressed full-length EGFR. Subsequent cDNA sequence analysis revealed the latter tumor as expressing an EGFR sequence variant with arginine, rather than leucine, at amino acid position 62; this was the only EGFR sequence variant identified among the 11 xenografts, other than the aforementioned vIII sequence variant. EGFR cDNAs were then examined from 12 more xenografts to determine whether additional missense sequence alterations were evident, and this analysis revealed one such case, expressing threonine, rather than alanine, at amino acid position 289 of the extracellular domain. This glioblastoma was also amplified for EGFR, but did not display significant erlotinib sensitivity, presumably due to its lacking PTEN expression. In total, our study identified two erlotinib-sensitive glioblastoma xenografts, with the common molecular characteristics shared by each being the expression of wild-type PTEN in combination with the expression of amplified and aberrant EGFR.

Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Publishing Authors By Initials

JN Sarkaria,L Yang,PT Grogan,GJ Kitange,BL Carlson,MA Schroeder,E Galanis,C Giannini,W Wu,EB Dinca,CD James,

For similar xenograft model antitumor assays research abstracts see: xenograft model antitumor assays research

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Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular cancer therapeutics

VOLUME: 6

Page Numbers: 1167-74

Journal Abbreviation: Mol. Cancer Ther.

ISSN: 1535-7163

DAY: 3

MONTH: Mar

YEAR: 2007

Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101132535

Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Keywords Mesh Terms:

KEYWORDS: Xenograft Model Antitumor Assays

MESH TERMS: metabolism

Chemical & Substance for Abstract: Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Information

Substance Name: PTEN Phosphohydrolase

Registry Number: EC 3.1.3.67

Grant and Affiliation Information for Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel.

AFFILIATION: Department of Neurological Surgery, University of California, San Francisco, Room HSW 792, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS 49720

ACRONYM: NS

MEDLINETA: Mol Cancer Ther

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