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