Inter-eye genomic heterogeneity in bilateral retinoblastoma via aqueous humor liquid biopsy

Elyssa Y Wong; Liya Xu; Lishuang Shen; Mary E Kim; Ashley Polski; Rishvanth K Prabakar; Rachana Shah; Rima Jubran; Jonathan W Kim; Jaclyn A Biegel; Xiaowu Gai; Peter Kuhn; James Hicks; Jesse L Berry

doi:10.1038/s41698-021-00212-0

Inter-eye genomic heterogeneity in bilateral retinoblastoma via aqueous humor liquid biopsy

NPJ Precis Oncol. 2021 Jul 27;5(1):73. doi: 10.1038/s41698-021-00212-0.

Authors

Elyssa Y Wong^#^{1

2}, Liya Xu^#^{1

3}, Lishuang Shen⁴, Mary E Kim^{1

2}, Ashley Polski^{1

2}, Rishvanth K Prabakar⁵, Rachana Shah⁶, Rima Jubran⁶, Jonathan W Kim^{1

2}, Jaclyn A Biegel^{4

7}, Xiaowu Gai^{4

7}, Peter Kuhn^{3

8

9

10}, James Hicks^{3

8

11}, Jesse L Berry^{12

13

14

15}

Affiliations

¹ The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA, USA.
² USC Roski Eye Institute, Keck School of Medicine of USC, Los Angeles, CA, USA.
³ Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA, USA.
⁴ Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
⁵ Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA, USA.
⁶ Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
⁷ Department of Pathology and Laboratory Medicine, Keck School of Medicine of USC, Los Angeles, CA, USA.
⁸ Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Los Angeles, CA, USA.
⁹ Department of Aerospace and Mechanical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
¹⁰ Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
¹¹ Department of Biochemistry and Molecular Medicine, Keck School of Medicine of USC, Los Angeles, CA, USA.
¹² The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA, USA. jesse.berry@med.usc.edu.
¹³ USC Roski Eye Institute, Keck School of Medicine of USC, Los Angeles, CA, USA. jesse.berry@med.usc.edu.
¹⁴ Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Los Angeles, CA, USA. jesse.berry@med.usc.edu.
¹⁵ The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA. jesse.berry@med.usc.edu.

^# Contributed equally.

Abstract

Germline alterations in the RB1 tumor suppressor gene predispose patients to develop retinoblastoma (RB) in both eyes. While similar treatment is given for each eye, there is often a variable therapeutic response between the eyes. Herein, we use the aqueous humor (AH) liquid biopsy to evaluate the cell-free tumor DNA (ctDNA) from each eye in a patient with bilateral RB. Despite the same predisposing germline RB1 mutation, AH analysis identified a different somatic RB1 mutation as well as separate and distinct chromosomal alterations in each eye. The longitudinal alterations in tumor fraction (TFx) corresponded to therapeutic responses in each eye. This case demonstrates that bilateral RB tumors develop separate genomic alterations, which may play a role in tumorigenesis and prognosis for eye salvage. Identifying these inter-eye differences without the need for enucleated tumor tissue may help direct active management of RB, with particular usefulness in bilateral cases.

Abstract

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