June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Inter-eye genomic heterogeneity in bilateral retinoblastoma via aqueous humor liquid biopsy
Author Affiliations & Notes
  • Elyssa Wong
    The Vision Center, Children's Hospital of Los Angeles, Los Angeles, California, United States
    Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • Liya Xu
    The Vision Center, Children's Hospital of Los Angeles, Los Angeles, California, United States
    Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California, United States
  • Lishuang Shen
    Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Mary E Kim
    The Vision Center, Children's Hospital of Los Angeles, Los Angeles, California, United States
    Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • Ashley Polski
    The Vision Center, Children's Hospital of Los Angeles, Los Angeles, California, United States
    Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • Rishvanth K. Prabakar
    Department of Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States
  • Rachana Shah
    Cancer and Blood Disease Institute, Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Rima Jubran
    Cancer and Blood Disease Institute, Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Jonathan Kim
    The Vision Center, Children's Hospital of Los Angeles, Los Angeles, California, United States
    Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • Jaclyn A. Biegel
    Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, Los Angeles, California, United States
    Department of Pathology and Laboratory Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • Xiaowu Gai
    Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, Los Angeles, California, United States
    Department of Pathology and Laboratory Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • Peter Kuhn
    Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California, United States
    Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • James Hicks
    Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California, United States
    Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • Jesse L Berry
    The Vision Center, Children's Hospital of Los Angeles, Los Angeles, California, United States
    Roski Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Elyssa Wong, None; Liya Xu, Provisional patent application: Aqueous Humor Cell Free DNA for Diagnostic and Prognostic Evaluation of Ophthalmic Disease (P); Lishuang Shen, None; Mary Kim, The Wright Foundation (F); Ashley Polski, None; Rishvanth K. Prabakar, None; Rachana Shah, None; Rima Jubran, None; Jonathan Kim, None; Jaclyn Biegel, None; Xiaowu Gai, None; Peter Kuhn, None; James Hicks, Provisional patent application: Aqueous Humor Cell Free DNA for Diagnostic and Prognostic Evaluation of Ophthalmic Disease (P); Jesse Berry, An unrestricted departmental grant from Research to Prevent Blindness (F), Hyundai Hope on Wheels Grant [RGA012351] (F), Provisional patent application: Aqueous Humor Cell Free DNA for Diagnostic and Prognostic Evaluation of Ophthalmic Disease (P), The Institute for Families, Inc., Children's Hospital Los Angeles (F), The Larry and Celia Moh Foundation (F), The National Cancer Institute Grant [P30CA014089] (F), The National Cancer Institute of the National Institute of Health Award Grant [K08CA232344] (F), The National Institute of Health Grant [P30EY029220] (F), The Wright Foundation (F)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2838. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Elyssa Wong, Liya Xu, Lishuang Shen, Mary E Kim, Ashley Polski, Rishvanth K. Prabakar, Rachana Shah, Rima Jubran, Jonathan Kim, Jaclyn A. Biegel, Xiaowu Gai, Peter Kuhn, James Hicks, Jesse L Berry; Inter-eye genomic heterogeneity in bilateral retinoblastoma via aqueous humor liquid biopsy. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2838.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Children with bilateral retinoblastoma (RB) receive similar treatments for each eye, however, there is often a variable therapeutic response between the eyes. Independent genomic events may occur during tumorigenesis in each eye, but these alterations are not fully understood. In this case report, we use the aqueous humor (AH) liquid biopsy to evaluate the cell-free tumor DNA (ctDNA) from each eye in a single patient with bilateral RB.

Methods : One patient with bilateral RB was included. Multiple samples of AH were obtained from each eye during routine intravitreal melphalan therapy and following enucleation of the left eye. Routine clinical blood testing was performed to determine germline RB1 status. CtDNA was isolated from the AH and sequenced on an Illumina platform to assess genome-wide somatic copy number alterations (SCNAs). The same sequencing libraries were used to identify somatic RB1 pathogenic variants using a custom hybridization and next generation sequencing panel targeting RB1. Tumor fraction (TFx) was estimated using ichorCNA software.

Results : Five AH samples from both eyes (3 from the right eye and 2 from the left eye) were included. Peripheral blood RB1 testing detected germline 13q and 16p deletions. Analysis of AH ctDNA identified a different somatic RB1 mutation and distinct SCNA profiles in each eye. Three SCNAs were consistently identified in all AH samples from the right eye; two SCNAs were detected in each AH sample derived from the left eye. The right eye was salvaged and TFx values in this eye decreased over the course of treatment. The left eye required enucleation due to tumor recurrence and demonstrated higher TFx values.

Conclusions : We present distinct inter-eye genomic profiles in a case of bilateral RB using the AH liquid biopsy. In addition, the longitudinal alterations in TFx corresponded to therapeutic response in each eye. Identifying inter-eye genomic heterogeneity without the need for enucleated tumor tissue may help direct active management of RB, with particular usefulness in bilateral cases.

This is a 2021 ARVO Annual Meeting abstract.

 

Fig 1. Right and left eyes of the same RB patient demonstrate different somatic RB1 mutations (A, B) and non-identical somatic copy number alterations (C, D).

Fig 1. Right and left eyes of the same RB patient demonstrate different somatic RB1 mutations (A, B) and non-identical somatic copy number alterations (C, D).

 

Fig 2. Salvage of the right eye corresponded to decrease in tumor fraction (TFx) (A, B, C). The left eye required enucleation and demonstrated high TFx value during therapy (D, E).

Fig 2. Salvage of the right eye corresponded to decrease in tumor fraction (TFx) (A, B, C). The left eye required enucleation and demonstrated high TFx value during therapy (D, E).

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×