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Correlating somatic copy number alteration in aqueous humour cfDNA with chemotherapy history, eye salvage and pathological features in retinoblastoma
  1. Yingxiu Luo1,2,
  2. Mingpeng Xu3,
  3. Ludi Yang1,2,
  4. Yiran Yao1,2,
  5. Jesse L Berry4,5,
  6. Liya Xu5,
  7. Xuyang Wen1,2,
  8. Xiaoyu He1,2,
  9. Minglei Han1,2,
  10. Xianqun Fan2,
  11. Jiayan Fan1,2,
  12. Renbing Jia1,2
  1. 1Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  2. 2Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
  3. 3Department of ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
  4. 4USC Roski Eye Institute,Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
  5. 5Vision Center at Children's Hospital Los Angeles, Los Angeles, California, USA
  1. Correspondence to Dr Renbing Jia, Department of Ophthalmology, Shanghai JiaoTong University School of Medicine, Shanghai, China; renbingjia{at}


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.

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  • 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.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.