Analysis of cytogenetic germline changes in Polish patients with retinoblastoma

Retinoblastoma, the most common eye tumor in children, can occur in hereditary or nonhereditary forms. In the hereditary form, various germline alterations, single nucleotide (SNVs) or copy number variations (CNVs) in the RB1 gene can be detected in patients. The aim of this study was to analyze cytogenetic germline changes in Polish patients with retinoblastoma and to assess whether cytogenetic techniques still have their application in diagnostics for retinoblastoma patients in the era of next-generation sequencing (NGS).

The results of genetic testing for germline mutations in patients with retinoblastoma performed between 2013 and 2023 were analyzed. In patients with cytogenetic alterations (CNV group, n = 19), the form of disease, age of onset, the first symptom, family history, and the type and extent of cytogenetic changes were verified. Comparative analyses were conducted between the CNV and SNV (n = 83) groups as well as the group of patients with normal genetic test results (n = 126).

Cytogenetic changes were detected in 19 probands. These included: 16 deletions (10 partial and 6 whole gene deletions), 2 duplications, and 1 balanced translocation. Partial gene deletions included from 1 to 16 exons. In the CNV group, bilateral involvement predominated, with strabismus being the most common initial symptom. The mean age of onset was 16.9 months (median = 11 months; IQR, 8-22 months) and was lower in patients with bilateral involvement and partial gene deletions. Statistically significant differences compared to patients with normal genetic test results were observed in terms of laterality, the age of onset, initial symptom, and the family history of retinoblastoma. No such differences were found between the CNV and SNV groups.

Cytogenetic changes constitute a significant part of germline alterations in patients with retinoblastoma. Cytogenetic techniques should still be considered in diagnostic protocols, especially in patients with bilateral involvement and/or positive family history, as well as in parents of patients with CNV.