Retinoblastoma
Retinoblastoma is the most common eye cancer of childhood and is defined by alteration of the RB1 gene. Around 40% of cases are heritable, which makes germline testing a standard part of the discussion rather than an optional extra.
Disease categories
Major disease categories
- Unilateral retinoblastoma
- Bilateral retinoblastoma
- Heritable retinoblastoma
- Trilateral retinoblastoma
Molecular
Molecular considerations
Biallelic RB1 alteration is definitional. A small subset is driven by MYCN amplification with intact RB1. Bilateral and multifocal disease essentially always indicates a germline RB1 alteration.
Markers commonly discussed in retinoblastoma
- RB1 (germline and somatic)
- MYCN amplification
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
RB1 testing is central to both diagnosis and family risk assessment.
Germline
Germline considerations
Germline RB1 testing is standard. A germline alteration carries implications for siblings, for future children, and for the child’s own lifetime risk of second primary cancers — which shapes long-term surveillance.
Molecular monitoring
ctDNA and liquid biopsy considerations
Aqueous humour analysis is an area of active research, since direct tumour biopsy is generally avoided in this disease.
Single-cell & computation
Single-cell and algorithmic approaches
Paediatric tumours are frequently driven by a single fusion or copy-number event on a quiet mutational background, which makes single-cell analysis unusually informative about developmental state rather than mutational burden. Single-cell RNA sequencing is used to place a tumour along a developmental trajectory. Algorithm work includes fusion detection, methylation classification, and analysis designed for the small cohort sizes that paediatric rarity imposes.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has germline RB1 testing been performed?
- Has bilateral or multifocal disease been excluded?
- Is long-term second-cancer surveillance planned where a germline alteration is present?
Resistance
Resistance and recurrence questions
- Has trilateral disease been considered in heritable cases?
Trials
Clinical trial considerations
Care and trials are concentrated at specialist paediatric ocular oncology centres.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.