March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
High Throughput Mass Spectrometry-based Mutation Profiling of Primary Uveal Melanoma
Author Affiliations & Notes
  • Anthony B. Daniels
    Department of Ophthalmology,
    Mass. Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • Joo-Eun Lee
    Ocular Molecular Genetics Institute,
    Mass. Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • Shan Lu
    Center for Cancer Genome Discovery, Dept. of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
  • Laura E. MacConaill
    Center for Cancer Genome Discovery, Dept. of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
  • Emanuele Palescandolo
    Center for Cancer Genome Discovery, Dept. of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
  • Scott M. Adams
    Ocular Molecular Genetics Institute,
    Mass. Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • Evangelos S. Gragoudas
    Department of Ophthalmology,
    Mass. Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • J. William Harbour
    Department of Ophthalmology and Visual Science, Washington University School of Medicine, St. Louis, Missouri
  • Levi A. Garraway
    Center for Cancer Genome Discovery, Dept. of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
  • Ivana K. Kim
    Department of Ophthalmology,
    Mass. Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Anthony B. Daniels, None; Joo-Eun Lee, None; Shan Lu, None; Laura E. MacConaill, None; Emanuele Palescandolo, None; Scott M. Adams, None; Evangelos S. Gragoudas, None; J. William Harbour, None; Levi A. Garraway, None; Ivana K. Kim, None
  • Footnotes
    Support  NIH grant CA139300, Research to Prevent Blindness, MEEI Melanoma Research Fund, Bacardi Fund
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5250. doi:
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      Anthony B. Daniels, Joo-Eun Lee, Shan Lu, Laura E. MacConaill, Emanuele Palescandolo, Scott M. Adams, Evangelos S. Gragoudas, J. William Harbour, Levi A. Garraway, Ivana K. Kim; High Throughput Mass Spectrometry-based Mutation Profiling of Primary Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5250.

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

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Abstract

Purpose: : To assess for mutations in a large number of oncogenes and tumor suppressor genes in primary uveal melanomas using a high-throughput profiling system.

Methods: : DNA was extracted and purified from fresh-frozen tissues or formalin-fixed, paraffin-embedded tissues from 124 untreated, primarily-enucleated large uveal melanomas. DNA was subjected to whole genome amplification and MALDI-TOF mass spectrometry-based mutation profiling (>1000 mutations tested across 120 oncogenes and tumor suppressor genes) using the OncoMap3 platform. All candidate mutations, as well as the GNAQ and GNA11 genes, were validated using homogeneous mass extend (hME) technology.

Results: : 98/124 (79%) samples (representing 89 unique tumors) passed all quality control steps and were assayed with the OncoMap platform. 58 mutation calls were made for 49 different mutations across 26 different genes in 34/98 (35%) samples. 93/102 samples (91%) that underwent hME validation harbored mutations in the GNAQ (46%) or GNA11 (45%) genes. hME validation revealed three samples with mutations in FGFR3 and two with mutations in EGFR. These additional mutations occurred exclusively in tumors that also had mutations in GNAQ or GNA11.

Conclusions: : The vast majority of primary large uveal melanomas harbor mutually-exclusive mutations in GNAQ or GNA11, but very rarely have mutations in other known oncogenes involved in the majority of other cancers. When present, these other mutations are only found in conjunction with GNAQ/GNA11 mutations, suggesting that these other mutations are likely not the prime drivers of oncogenesis in uveal melanoma. OncoMap3 mutation profiling is an effective means of screening large numbers of oncogenes in large numbers of tumor samples.

Keywords: tumors • melanoma • genetics 
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