New Retinoblastoma research breakthrough with aqueous humor cell-free DNA analysis
Sara Taghizadeh1 , Fariba Ghassemi1 *, Seyed Farzad Mohammadi1
- Translational Ophthalmology Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences
Abstract: Retinoblastoma (RB) is the most common intraocular malignancy afflicting children.
The retinoblastoma susceptibility gene RB1 is a tumor-suppressing that encodes a protein with a regulatory role in the cellular growth cycle at the G1 checkpoint. Both alleles of the retinoblastoma gene have to be inactivated in both germline and somatic types for tumor development.
The distinction between germline and somatic mutations is vital, as germline cases need close monitoring with short-term risk of new ocular tumors and long-term risk of second systemic cancers. Confirming the non-heritable nature of the retinoblastoma can keep away from screening examinations in many family members, with extensive price financial savings and keep away from plausible morbidity in unaffected family members, formerly screened unnecessarily.
Methods: This review searches for the medical utility of aqueous humor (AH) liquid biopsy for RB at diagnosis and longitudinally during therapy for its: diagnostic value, prognostic significance, and possible future application to a precision oncology model to direct personalized management of RB.
Results: This novel method ultimately allows for the identification of tumor-derived molecular biomarkers in RB eyes without invasive tumor biopsy or enucleation. The AH liquid biopsy opens the door to apply a long time of knowledge about RB genomics in an impactful clinical application and to better understand intra-tumoral dynamics during therapy.
Conclusion: This review demonstrates the feasibility of testing AH samples in non-enucleated eyes, with AH cell-free DNA (cfDNA) enabling detection of somatic variants in patients undergoing intravitreal chemotherapy (IVC) where the tumor is not available. Capture-based technology was used to identify previously undetected RB1 gene mutations and loss of heterozygote (LOH) alterations in AH cfDNA.
Also, the majority of cfDNA in the AH is from the tumor due to the compartmentalized nature of ocular fluids, a factor that facilitates this test. Among the enucleated eyes tested, higher amounts of cfDNA were seen in eyes undergoing primary enucleation. Adequate but lower DNA levels were present in eyes treated with systemic chemotherapy and local treatment such as laser and cryotherapy. This would suggest the cfDNA load varies with the tumor load.
