Cell Free DNA (cfDNA) in the Blood of Retinoblastoma Patients The Robert M. Ellsworth Lecture

ABSTRACT

Background

Cell-free DNA analysis in cancer has gone from research to widespread clinical use in the past 10 years. At Memorial Sloan Kettering Cancer Center, we developed a technology and test to assay cell-free DNA (cfDNA) from blood (plasma) in our retinoblastoma patients.

Results

cfDNA derived from intraocular retinoblastoma can be measured and quantified in the blood (plasma) of patients. It is derived from the tumor cells themselves. Simulating lesions did not have cfDNA abnormalities. cfDNA disappears quickly after cutting the optic nerve (50% gone in 10 minutes) and if cfDNA is measurable after enucleation, metastases develop. Analysis of the buffy coat can detect germline defects including very low levels of mosaicism not detected with other NGS techniques. Analysis of the buffy coat also reveals non Rb1 germline predilections to second cancers.

Conclusion

Analysis of cfDNA from blood of retinoblastoma patients can be used to diagnose and manage retinoblastoma and reflect an accurate molecular profile of RB1 abnormalities of the intraocular tumor. Analysis of the germline with the buffy coat detects very low levels of mosaicism not detected with conventional methods. Liquid biopsy for retinoblastoma is already in clinical use and offers information not available with any other technique.

KEYWORDS:

• Retinoblastoma
• cancer
• cfDNA
• ctDNA
• access
• impact
• intraarterial chemotherapy
• enucleation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the The Fund for Ophthalmic Knowledge, Inc” NY, NY; NIH [P30 CA008748]; The Gerber Foundation.