June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Aqueous Humor as a Surrogate Liquid Tumor Biopsy in Retinoblastoma
Author Affiliations & Notes
  • Jesse L Berry
    USC Roski Eye Institute, Los Angeles, California, United States
    Ophthalmology, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Liya Xu
    University of Southern California, Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, Los Angeles, California, United States
  • Kevin Stachelek
    Ophthalmology, Children's Hospital Los Angeles, Los Angeles, California, United States
  • A. Linn Murphree
    Ophthalmology, Children's Hospital Los Angeles, Los Angeles, California, United States
    USC Roski Eye Institute, Los Angeles, California, United States
  • Emily Zolfoghari
    Ophthalmology, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Kathleen McGovern
    Ophthalmology, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Thomas Lee
    Ophthalmology, Children's Hospital Los Angeles, Los Angeles, California, United States
    USC Roski Eye Institute, Los Angeles, California, United States
  • Anders Carlsson
    University of Southern California, Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, Los Angeles, California, United States
  • Peter Kuhn
    University of Southern California, Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, California, United States
    University of Southern California, Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, Los Angeles, California, United States
  • Jonathan Kim
    USC Roski Eye Institute, Los Angeles, California, United States
    Ophthalmology, Children's Hospital Los Angeles, Los Angeles, California, United States
  • David Cobrinik
    Ophthalmology, Children's Hospital Los Angeles, Los Angeles, California, United States
    USC Roski Eye Institute, Los Angeles, California, United States
  • James Hicks
    University of Southern California, Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, California, United States
    University of Southern California, Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Jesse Berry, None; Liya Xu, None; Kevin Stachelek, None; A. Linn Murphree, None; Emily Zolfoghari, None; Kathleen McGovern, None; Thomas Lee, None; Anders Carlsson, None; Peter Kuhn, None; Jonathan Kim, None; David Cobrinik, None; James Hicks, None
  • Footnotes
    Support  Nautica Foundation
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 856. doi:
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    • Get Citation

      Jesse L Berry, Liya Xu, Kevin Stachelek, A. Linn Murphree, Emily Zolfoghari, Kathleen McGovern, Thomas Lee, Anders Carlsson, Peter Kuhn, Jonathan Kim, David Cobrinik, James Hicks; Aqueous Humor as a Surrogate Liquid Tumor Biopsy in Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2017;58(8):856.

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

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Abstract

Purpose : The aim of this study is to determine whether tumor-derived nucleic acids and tumor DNA copy number alterations can be detected in the aqueous humor (AH) of retinoblastoma (RB) eyes.

Methods : AH was analyzed for DNA, RNA and miRNA using Qubit HS kits. Circulating cell-free DNA (cfDNA) isolation and sequencing library protocols were optimized to retain cfDNAs from the AH and these optimized methods were applied to AH samples from RB patients. Shallow whole genome sequencing was performed on Illumina platform followed by genome-wide copy number variation (CNV) profiling to assess the presence of tumor DNA fractions in AH cfDNA.

Results : Eighteen AH samples from 8 patients (6 patients pre-intravitreal injection and 2 post-enucleation) were examined. All had measurable DNA, RNA and miRNA, with miRNA having the highest concentrations. Whole genome sequencing of AH cfDNA from 2 primarily enucleated eyes and sequential AH cfDNAs obtained from 2 eyes undergoing intravitreal melphalan injections for treatment of tumor seeding revealed tumor-derived cfDNA based on CNV profiles that demonstrated tumor copy number alterations.

Conclusions : This is the first study to evaluate AH from RB eyes undergoing salvage therapy with intravitreal injection of melphalan. We were able to assay quantifiable levels of nucleic acids in treated and untreated eyes and found that AH cfDNA had retinoblastoma-related DNA copy number alterations in all four tested RB patients. This suggests that AH can serve as a ‘surrogate tumor biopsy’ when tumor tissue is not available.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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