September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Comprehensive Genomic Profiling of Orbital and Ocular Adnexal Lymphomas Identifies Frequent Alterations in MYD88 and Chromatin Modifiers: New Routes to Targeted Therapies
Author Affiliations & Notes
  • Rajesh C Rao
    University of Michigan, Ann Arbor, Michigan, United States
    Ophthalmology, VA Ann Arbor Healthsystem, Ann Arbor, Michigan, United States
  • Andi Cani
    University of Michigan, Ann Arbor, Michigan, United States
  • Moaaz Soliman
    University of Michigan, Ann Arbor, Michigan, United States
  • Daniel H Hovelson
    University of Michigan, Ann Arbor, Michigan, United States
  • Chia-Jen Liu
    University of Michigan, Ann Arbor, Michigan, United States
  • Andrew S. McDaniel
    University of Michigan, Ann Arbor, Michigan, United States
  • Michaela J. Haller
    University of Michigan, Ann Arbor, Michigan, United States
  • Jarred Bratley
    University of Michigan, Ann Arbor, Michigan, United States
  • Samantha Rahrig
    University of Michigan, Ann Arbor, Michigan, United States
  • Cesar A. Briceno
    University of Michigan, Ann Arbor, Michigan, United States
  • Scott A. Tomlins
    University of Michigan, Ann Arbor, Michigan, United States
  • Footnotes
    Commercial Relationships   Rajesh Rao, None; Andi Cani, None; Moaaz Soliman, None; Daniel Hovelson, None; Chia-Jen Liu, None; Andrew McDaniel, None; Michaela Haller, None; Jarred Bratley, None; Samantha Rahrig, None; Cesar Briceno, None; Scott Tomlins, Compendia Bioscience/Life Technologies/ThermoFisher Scientific (F)
  • Footnotes
    Support  NIH Grant EY022299, March Hoops to Beat Blindness, Leonard G. Miller Ophthalmic Research Fund at the Kellogg Eye Center, Leslie H. and Abigail S. Wexner Emerging Scholar of the A. Alfred Taubman Medical Research Institute
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4089. doi:
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      Rajesh C Rao, Andi Cani, Moaaz Soliman, Daniel H Hovelson, Chia-Jen Liu, Andrew S. McDaniel, Michaela J. Haller, Jarred Bratley, Samantha Rahrig, Cesar A. Briceno, Scott A. Tomlins; Comprehensive Genomic Profiling of Orbital and Ocular Adnexal Lymphomas Identifies Frequent Alterations in MYD88 and Chromatin Modifiers: New Routes to Targeted Therapies. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4089.

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

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Abstract

Purpose : Non-Hodgkin lymphomas of the eye and surrounding tissues (orbital and ocular adnexal lymphomas, OOALs) are the most common primary orbital malignancy, are increasing in incidence in some populations, and often have high relapse rates and toxicity from localized treatment. Despite recent advances in genomic profiling and precision medicine of cancer in general, orbital tumors remain poorly characterized molecularly.

Methods : We performed targeted next generation sequencing (NGS) profiling of 38 OOAL formalin-fixed paraffin-embedded (FFPE) specimens obtained from a single academic ophthalmology clinic using a panel targeting near-term clinically relevant genes. This panel used is part of the NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) , a clinical trial that has enrolled adults 18 years of age and older with advanced solid tumors and lymphomas that are no longer responding (or never responded) to standard therapy and have begun to grow.

Results : Potentially actionable mutations and copy number alterations (CNAs) were prioritized based on gain- and loss-of function (GoF and LoF, respectively) analyses and catalogued approved and investigational therapies. Of 36 informative samples, 53% harbored a prioritized alteration (median of 1, range 0-5 per sample). MYD88 was the most frequently altered gene in our cohort, with potentially clinically relevant hot-spot GoF mutations identified in 28% of OOALs. Prioritized alterations in epigenetic modulators were common and included GoF EZH2 mutations (of clinical importance) and LoF ARID1A mutations (both in 8% of OOALs). Single prioritized alterations were also identified in the histone methyltransferases KMT2B and KMT3B. Lastly, LoF mutations and CNAs in the tumor suppressors TP53, CDKN2A, PTEN, ATM and NF1, as well as GoF mutations in the oncogenes HRAS and NRAS were also observed.

Conclusions : Taken together, our study demonstrates that NGS can be used to profile routine OOAL FFPE tissue for identification of somatic driving alterations and nomination of potential therapeutic strategies.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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