Article Text
Background
This study determined to probe the potential association between somatic copy number alteration (SCNA) in retinoblastoma (RB) aqueous humour (AH) and pathological high-risk factors, clinical features and previous chemotherapy history.
Methods Single-centre retrospective cohort study from including 58 AH samples collected from 58 patients diagnosed. Among them, 41 samples were collected after enucleation and 17 samples were collected before intravitreal chemotherapy. SCNAs were accessed by conducting shallow whole-genome sequencing in cell-free (cf) DNA of AH. HRs and ORs were applied to measure risk factors.
Results Canonical RB SCNAs including 1q gain (87%), 2p gain (50%), 6p gain (76%), 16q loss (69%) were frequently detected. Non-classical RB SCNAs in AH including 17q gain (53%), 19q loss (43%), 7q gain (35%) were also commonly observed. 19q loss was significantly more common in patients with cT3c or worse stage than others (p=0.034). 2p gain(p=0.001) and 7q gain(p=0.001) were both more common in patients with primary enucleation than those with previous chemotherapy. Interestingly, both 2p gain (HR=1.933, p=0.027) and 7q gain (HR=2.394, p=0.005) might predict enucleation. Correlation analysis with pathological features among enucleated eyes showed that 19q loss can predict a higher risk for both massive choroid invasion (OR=4.909, p=0.038) and postlaminar optic nerve invasion (OR=4.250, p=0.043).
Discussion Sequencing of AH cfDNA in RB can provide sufficient in vivo information. 19q loss was a potential signature of advanced cases clinically and pathologically.
Repeated sampling from eyes receiving sequential chemotherapy should be conducted to evaluate fluctuation of SCNA in future study.
- Aqueous humour
- Pathology
- Neoplasia
Data availability statement
Data are available on reasonable request.
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Data availability statement
Data are available on reasonable request.
Footnotes
Contributors Concept and study design: XF and RJ. Sample collection: MH and JF. Clinical data collection: YL and MX. Experiments: LY, YY, XW and XH. Data analysis and interpretation: YL, ML and LY. Manuscript writing: YL. Review and approval of the manuscript: all authors. Guarantor: RJ
Funding This work was supported by National Natural Science Foundation of China (grant 81570884, 81872339, 82272642), Shanghai Municipal Science and Technology Major Project (17JC1420100), Shanghai Municipal Science and Technology Major Project (19JC1410202), Shanghai Science and Technology Development Funds (Grant 17DZ2260100, 19QA1405100), Shanghai Youth Top-notch Talent Support Programme and Shanghai Ninth People’s Hospital Excellent Youth Fund Programme (JYYQ003).
Disclaimer The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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