journal contribution
posted on 2023-04-03, 17:21 authored by Jesse L. Berry, Liya Xu, Irsan Kooi, A. Linn Murphree, Rishvanth K. Prabakar, Mark Reid, Kevin Stachelek, Bao Han A. Le, Lisa Welter, Bibiana J. Reiser, Patricia Chévez-Barrios, Rima Jubran, Thomas C. Lee, Jonathan W. Kim, Peter Kuhn, David Cobrinik, James Hicks Supplemental Figure 5, online only: Copy Number Alteration (CNA) profiles from Case 11, 21, and 25 demonstrating change in amplitude of the alterations in longitudinal AH samples taken over time. Case 11 showed a progressive gain of 6p and was eventually enucleated whereas Cases 21 and 25 showed a decrease in the amplitude of alterations and these eyes were salvaged.
Funding
Knights Templar Eye Foundation
The Larry and Celia Moh Foundation
The Institute for Families, Inc.
Children's Hospital Los Angeles
Vicky Joseph Research Fund
Carol Vassiliadis Research Fund
NCI of the NIH
History
ARTICLE ABSTRACT
Tumor-derived cell-free DNA (cfDNA) has biomarker potential; therefore, this study aimed to identify cfDNA in the aqueous humor (AH) of retinoblastoma eyes and correlate somatic chromosomal copy-number alterations (SCNA) with clinical outcomes, specifically eye salvage. AH was extracted via paracentesis during intravitreal injection of chemotherapy or enucleation. Shallow whole-genome sequencing was performed using isolated cfDNA to assess for highly recurrent SCNAs in retinoblastoma including gain of 1q, 2p, 6p, loss of 13q, 16q, and focal MYCN amplification. Sixty-three clinical specimens of AH from 29 eyes of 26 patients were evaluated; 13 eyes were enucleated and 16 were salvaged (e.g., saved). The presence of detectable SCNAs was 92% in enucleated eyes versus 38% in salvaged eyes (P = 0.006). Gain of chromosome 6p was the most common SCNA found in 77% of enucleated eyes, compared with 25% of salvaged eyes (P = 0.0092), and associated with a 10-fold increased odds of enucleation (OR, 10; 95% CI, 1.8–55.6). The median amplitude of 6p gain was 1.47 in enucleated versus 1.07 in salvaged eyes (P = 0.001). The presence of AH SCNAs was correlated retrospectively with eye salvage. The probability of ocular salvage was higher in eyes without detectable SCNAs in the AH (P = 0.0028), specifically 6p gain. This is the first study to correlate clinical outcomes with SCNAs in the AH from retinoblastoma eyes, as such these findings indicate that 6p gain in the aqueous humor is a potential prognostic biomarker for poor clinical response to therapy.Implications: The correlation of clinical outcomes and SCNAs in the AH identified in the current study requires prospective studies to validate these finding before SCNAs, like 6p gain, can be used to predict clinical outcomes at diagnosis. Mol Cancer Res; 16(11); 1701–12. ©2018 AACR.
