April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Modeling Mitogen-activated Protein Kinase Pathway Activity In Novel Uveal Melanoma Cell Lines
Author Affiliations & Notes
  • Barry L. Burgess
    Ophthalmology, UCLA/Jules Stein Eye Institute, Los Angeles, California
  • Antoni Ribas
    Hematology/Oncology, UCLA/Jonssen Comprehensive Cancer Center, Los Angeles, California
  • Erika Von Euw
    Hematology/Oncology, UCLA/Jonssen Comprehensive Cancer Center, Los Angeles, California
  • Tara A. McCannel
    Ophthalmology, UCLA/Jules Stein Eye Institute, Los Angeles, California
  • Footnotes
    Commercial Relationships  Barry L. Burgess, None; Antoni Ribas, None; Erika Von Euw, None; Tara A. McCannel, None
  • Footnotes
    Support  George E. and Ruth Moss Trust
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1442. doi:
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      Barry L. Burgess, Antoni Ribas, Erika Von Euw, Tara A. McCannel; Modeling Mitogen-activated Protein Kinase Pathway Activity In Novel Uveal Melanoma Cell Lines. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1442.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To model the functional relationships between chromosome copy number, gene expression, somatic mutations and the mitogen-activated protein kinase (MAPK) pathway in novel uveal melanoma cell lines.

Methods: : Primary and metastatic uveal melanomas sampled by fine needle aspiration biopsy were evaluated by mapping array, expression array and resequencing. Cell lines derived from those biopsies were analyzed for similarity to their source tumors and were evaluated for MAPK pathway activity.

Results: : Four cell lines from primary uveal melanoma with metastatic outcome and one cell line from a liver metastasis were successfully propagated and evaluated. Each had cytogenetic findings of monosomy 3, 6q loss, 8p loss, 8q gain, and 16q loss. The liver lesion cell line demonstrated isodisomy 3. Each cell line had a gene expression profile similar to the corresponding tumor sample. Each cell line had a single heterozygous, somatic, activating mutation in either GNAQ or GNA11 occurring at codon 209, resulting in Q209L or Q209P. Each cell line was positive for pMEK and pERK activity and each was sensitive to sub-nanomolar concentrations of the MEK inhibitors AZD6244 and TAK733.

Conclusions: : Cell lines derived from fine needle aspirate biopsy provide a stable source of material for examining the relationships of cytogenetic aberrations and driver mutations to MAPK pathway activity.

Keywords: melanoma • tumors • mutations 
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