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.
Highlights
Retinoblastoma (RB) is an eye cancer that forms in the developing retina and affects approximately 8,000 infants and toddlers each year worldwide[1]
We have demonstrated that the aqueous humor (AH) is a rich source of cell-free tumorderived DNA that captures the genomic landscape of RB tumors, including RB1 mutations and RB SCNAs10,11
Using an AH-based liquid biopsy avoids the need for enucleated tumor tissue and enables longitudinal monitoring of molecular tumor dynamics during active globe-conserving therapy for each eye
Summary
Retinoblastoma (RB) is an eye cancer that forms in the developing retina and affects approximately 8,000 infants and toddlers each year worldwide[1]. Despite the same predisposing germline RB1 mutation and similar treatment, there is frequently a variable therapeutic response between each eye of the same patient This is likely due to differences at the molecular level between the tumors in each eye. Further characterizations of independent heterogenous inter-eye events in bilateral RB patients are limited given 1) the goal of avoiding bilateral enucleation and 2) the aforementioned contraindication to direct tumor biopsy of RB6. To overcome this problem, we utilize the aqueous humor (AH), the clear fluid that circulates in the front of the eye, as a liquid biopsy for RB.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
