Genetic Diagnosis of Retinoblastoma Using Aqueous Humour—Findings from an Extended Cohort
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Sample Collection
- From primary (PE) or secondary (SE) enucleated eyes prior to opening the eye for tumour dissection;
- During IViC via the standard clinical protocol of AH aspiration prior to chemotherapy injection (Tx);
- By diagnostic anterior chamber tap from retained eyes that had received a minimum of one cycle of intravenous (IVC) or intra-arterial (IAC) chemotherapy (Dx1+).
2.2. Sample Processing and Analysis
2.3. Previous Publication of Data
2.4. Statistical Analysis
2.5. Clinical Diagnostic Testing
3. Results
3.1. Patient and Sample Characteristics
3.2. Cell-Free DNA Concentration in Aqueous Humour
3.3. RB1 Pathogenic Variant Detection Using Aqueous Humour
3.3.1. RB1 Pathogenic Variant Detection in AH from Enucleated Eyes
Primary Enucleation (PE)
Secondary Enucleation (SE)
3.3.2. RB1 Pathogenic Variant Detection in AH from Eyes Undergoing Conservative Treatment
Anterior Chamber Tap (Dx1+)
Eyes Undergoing IViC (Tx)
3.4. Determining Tumour-Derived Fraction of Cell-Free DNA
3.5. RB1 Pathogenic Variant Detection Correlates with cfDNA Concentration
3.6. Comparison of cfDNA Concentration and RB1 Pathogenic Variant Detection in Serial AH Samples
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Correction Statement
Appendix A
Appendix A.1. Sample Processing and DNA Extraction
Appendix A.2. Targeted NGS
Appendix A.3. Bioinformatic Analysis
References
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Sample Type | Samples (n) | Patients/Eyes (n) | Laterality U/B (n) | IIRC Grade C/D/E (n) | Chemotherapy Cycles 1 Mean (Range) |
---|---|---|---|---|---|
PE | 27 | 27/27 | 21/6 | 0/9/18 | 0 |
Dx1+ | 14 | 14/14 | 13/1 | 5/7/2 | 1.6 (1–3) |
Tx | 27 | 26/27 | 17/9 | 2/19/6 | 5.7 (2–12) |
SE | 7 | 7/7 | 2/5 | 0/4/3 | 5.5 (2–8) |
All | 75 | 68/71 | 49/19 | 6/38/27 | 2.8 (0–12) |
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Share and Cite
Gerrish, A.; Mashayamombe-Wolfgarten, C.; Stone, E.; Román-Montañana, C.; Abbott, J.; Jenkinson, H.; Millen, G.; Gurney, S.; McCalla, M.; Staveley, S.-J.; et al. Genetic Diagnosis of Retinoblastoma Using Aqueous Humour—Findings from an Extended Cohort. Cancers 2024, 16, 1565. https://doi.org/10.3390/cancers16081565
Gerrish A, Mashayamombe-Wolfgarten C, Stone E, Román-Montañana C, Abbott J, Jenkinson H, Millen G, Gurney S, McCalla M, Staveley S-J, et al. Genetic Diagnosis of Retinoblastoma Using Aqueous Humour—Findings from an Extended Cohort. Cancers. 2024; 16(8):1565. https://doi.org/10.3390/cancers16081565
Chicago/Turabian StyleGerrish, Amy, Chipo Mashayamombe-Wolfgarten, Edward Stone, Claudia Román-Montañana, Joseph Abbott, Helen Jenkinson, Gerard Millen, Sam Gurney, Maureen McCalla, Sarah-Jane Staveley, and et al. 2024. "Genetic Diagnosis of Retinoblastoma Using Aqueous Humour—Findings from an Extended Cohort" Cancers 16, no. 8: 1565. https://doi.org/10.3390/cancers16081565