Abstract
Purpose :
Retinoblastoma (RB) is the most common ocular tumor of the child, in most instances initiated by mutations in the RB1 gene. Molecular biomarkers determining its aggressiveness and progression have so far only been partially elucidated, due to a significant risk of tumor cells’ dissemination following classical biopsies. Recently, the so-called “liquid biopsies” from the aqueous humor (AH) have demonstrated to be a valid alternative to direct tissue sampling for retinoblastoma. By sequencing tumor cell-free DNA (cfDNA) from the AH, we aim to gain insights into the genetic makeup of retinoblastoma and relate specific genotypes to clinical outcomes, such as tumor aggressiveness and therapeutic response.
Methods :
Following the collection of approximately 100ul of AH, cfDNA was isolated, and genetic analysis was performed by whole-genome sequencing (WGS) and whole-exome sequencing (WES). Raw data were analyzed with an internal pipeline for the identification of mutations, including single-base variants and genomic copy number variations.
Results :
We completed a proof-of-concept analysis on a small set of 5 AHs, and we are now performing the analysis on the bulk of our collection, consisting in approximately 370 samples. Our preliminary results show a considerable genetic heterogeneity of somatic variations in different tumors, despite the relatively small fraction of samples that were sequenced. Nevertheless, we also found some recurrent genomic alterations, such as 1q gain, 16q loss, and 6p gain.
Conclusions :
Overall, our data indicate that retinoblastoma is more diverse at the genetic level than previously thought, and that such heterogeneity may shape in the end its clinical characteristics.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.