Spectrum of Germline Cytogenomic Alterations in RB1 in Mexican Patients With Retinoblastoma

The aim of this study was to characterize the spectrum of germline cytogenomic alterations in RB1 in Mexican patients with retinoblastoma.

Genomic DNA was isolated from peripheral blood from 88 Mexican patients with retinoblastoma RB (56 unilateral and 32 bilateral) treated at the Civil Hospital of Guadalajara between 2014 and 2024. Single nucleotide variants (SNVs) were analyzed by next generation sequencing (NGS) using a custom RB1 panel. Large RB1 deletions were assessed by multiplex ligation-dependent probe amplification (MLPA), whereas fluorescence in situ hybridization (FISH) and G-banding karyotyping were applied following a hierarchical workflow based on institutional resources to identify deletions at 13q14.

Germline cytogenomic alterations were identified in 37 of the 88 patients (42.1%). Among these, 30 had bilateral RB and 7 had unilateral RB. Detection rates were 93.7% (30/32) in bilateral cases and 12.5% (7/56) in unilateral cases. Of the total cytogenomic alterations, 72.9% (27/37) were SNVs and 27.1% (10/37) were large deletions.

This study provides an overview of the spectrum of germline cytogenetic alterations and clinical features in Mexican patients with RB. Our results expand the understanding of RB in this population and underscore the need for multimodal approaches for the detection and functional characterization of RB1 alterations. This study reports the largest Mexican retinoblastoma cohort with comprehensive germline RB1 characterization and high detection rates, particularly in bilateral disease.