June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
A multicenter analysis of nucleic acid quantification using aqueous humor liquid biopsy in retinoblastoma – Implications for clinical testing
Author Affiliations & Notes
  • Liya Xu
    Children's Hospital Los Angeles, Los Angeles, California, United States
    University of Southern California, Los Angeles, California, United States
  • Deborah Im
    Children's Hospital Los Angeles, Los Angeles, California, United States
    University of Southern California, Los Angeles, California, United States
  • Sarah Pike
    Children's Hospital Los Angeles, Los Angeles, California, United States
    University of Southern California, Los Angeles, California, United States
  • Mark Reid
    Children's Hospital Los Angeles, Los Angeles, California, United States
  • Chen-Ching Peng
    Children's Hospital Los Angeles, Los Angeles, California, United States
  • Hans E Grossniklaus
    Emory University School of Medicine, Atlanta, Georgia, United States
  • G. Baker Hubbard
    Emory University School of Medicine, Atlanta, Georgia, United States
  • Alison Skalet
    Oregon Health & Science University, Portland, Oregon, United States
  • Carol L. Shields
    Thomas Jefferson University, Philadelphia, Pennsylvania, United States
    Wills Eye Hospital, Philadelphia, Pennsylvania, United States
  • Sarah E. Lally
    Thomas Jefferson University, Philadelphia, Pennsylvania, United States
    Wills Eye Hospital, Philadelphia, Pennsylvania, United States
  • Andrew W Stacey
    Seattle Children's Hospital, Seattle, Washington, United States
  • Bibiana J. Reiser
    Children's Hospital Los Angeles, Los Angeles, California, United States
    University of Southern California, Los Angeles, California, United States
  • Aaron Nagiel
    Children's Hospital Los Angeles, Los Angeles, California, United States
    University of Southern California, Los Angeles, California, United States
  • Rachana Shah
    Children's Hospital Los Angeles, Los Angeles, California, United States
    University of Southern California, Los Angeles, California, United States
  • Jesse L Berry
    Children's Hospital Los Angeles, Los Angeles, California, United States
    University of Southern California, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Liya Xu CHLA, Code P (Patent); Deborah Im None; Sarah Pike None; Mark Reid None; Chen-Ching Peng None; Hans Grossniklaus None; G. Baker Hubbard None; Alison Skalet None; Carol Shields None; Sarah Lally None; Andrew Stacey None; Bibiana Reiser None; Aaron Nagiel None; Rachana Shah None; Jesse Berry CHLA, Code P (Patent)
  • Footnotes
    Support  Dr. Jesse L. Berry has research support from: National Cancer Institute of the National Institute of Health Award Number K08CA232344, The Wright Foundation, Children’s Oncology Group/ St. Baldrick’s Foundation, Danhakl Family Foundation, Hyundai Hope on Wheels, Childhood Eye Cancer Trust, Children’s Cancer Research Fund, A. Linn Murphree, MD, Chair in Ocular Oncology, The Berle & Lucy Adams Chair in Cancer Research, The Larry and Celia Moh Foundation, The Institute for Families, Inc., Children's Hospital Los Angeles. Dr. Liya Xu has research support from The Knights Templar Eye Foundation.
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1258. doi:
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    • Get Citation

      Liya Xu, Deborah Im, Sarah Pike, Mark Reid, Chen-Ching Peng, Hans E Grossniklaus, G. Baker Hubbard, Alison Skalet, Carol L. Shields, Sarah E. Lally, Andrew W Stacey, Bibiana J. Reiser, Aaron Nagiel, Rachana Shah, Jesse L Berry; A multicenter analysis of nucleic acid quantification using aqueous humor liquid biopsy in retinoblastoma – Implications for clinical testing. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1258.

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

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Abstract

Purpose : Retinoblastoma (RB) is most often diagnosed with clinical features and not diagnosed with a tumor biopsy. This study describes tumor-derived analyte concentrations from aqueous humor (AH) liquid biopsy and its use in clinical assays.

Methods : 128 RB AH samples, taken from treatment naïve (TN) eyes, those undergoing treatment (TX), after completing treatment (END) and during bevacizumab injection for radiation therapy after completing RB treatment (BEV), and 14 control AH were analyzed for unprocessed analytes (dsDNA, ssDNA, miRNA, RNA, and protein) with Qubit fluorescence assays. dsDNA from two RB samples underwent shallow whole-genome sequencing (LP-WGS) to detect somatic copy number alterations (SCNAs). Logistic regression was used to predict disease burden given analyte concentrations.

Results : Results revealed dsDNA, ssDNA, miRNA, and proteins, but not RNA, were quantifiable in most samples (up to 98%) with Qubit fluorescence assays. Median dsDNA concentration was significantly higher in TN (3.08 ng/L) compared to TX (0.18 ng/L; P<0.0001) at an order of 17 times greater, and 20 times greater than END samples (0.15 ng/L; P=0.001). Using logistic regression, nucleic acid concentrations were useful in predicting higher versus lower RB disease burden. RB SCNAs were identified in a TX, but not in a BEV sample, indicating the correlation with retinoblastoma activity.

Conclusions : AH liquid biopsy in RB is a high yield source of dsDNA, ssDNA, miRNA and protein. TN samples are most useful for RB1 mutational analyses. Genomic analysis may be more informative of tumor activity status than quantification alone, and can be performed even with smaller analyte concentrations obtained from TX samples.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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