David H Abramson1,2. 1. Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA. 2. Department of Ophthalmology, Weill Cornell Medical School, New York, New York, USA.
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.
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.
Authors: Danielle Novetsky Friedman; Meier Hsu; Chaya S Moskowitz; Jasmine H Francis; Eric Lis; Megan Harlan Fleischut; Kevin C Oeffinger; Michael Walsh; Emily S Tonorezos; Charles A Sklar; David H Abramson; Ira J Dunkel Journal: Pediatr Blood Cancer Date: 2020-05-09 Impact factor: 3.167
Authors: C Eng; F P Li; D H Abramson; R M Ellsworth; F L Wong; M B Goldman; J Seddon; N Tarbell; J D Boice Journal: J Natl Cancer Inst Date: 1993-07-21 Impact factor: 13.506
Authors: Jonathan E Lu; Jasmine H Francis; Ira J Dunkel; Carol L Shields; Michael D Yu; Jesse L Berry; Kaitlin Kogachi; Alison H Skalet; Audra K Miller; Pranav R Santapuram; Anthony B Daniels; David H Abramson Journal: Br J Ophthalmol Date: 2018-10-25 Impact factor: 4.638
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Authors: Elise M Fiala; Gowtham Jayakumaran; Audrey Mauguen; Jennifer A Kennedy; Nancy Bouvier; Yelena Kemel; Megan Harlan Fleischut; Anna Maio; Erin E Salo-Mullen; Margaret Sheehan; Angela G Arnold; Alicia Latham; Maria I Carlo; Karen Cadoo; Semanti Murkherjee; Emily K Slotkin; Tanya Trippett; Julia Glade Bender; Paul A Meyers; Leonard Wexler; Filemon S Dela Cruz; Nai-Kong Cheung; Ellen Basu; Alex Kentsis; Michael Ortiz; Jasmine H Francis; Ira J Dunkel; Yasmin Khakoo; Stephen Gilheeney; Sameer Farouk Sait; Christopher J Forlenza; Maria Sulis; Matthias Karajannis; Shakeel Modak; Justin T Gerstle; Todd E Heaton; Stephen Roberts; Ciyu Yang; Sowmya Jairam; Joseph Vijai; Sabine Topka; Danielle N Friedman; Zsofia K Stadler; Mark Robson; Michael F Berger; Nikolaus Schultz; Marc Ladanyi; Richard J O'Reilly; David H Abramson; Ozge Ceyhan-Birsoy; Liying Zhang; Diana Mandelker; Neerav N Shukla; Andrew L Kung; Kenneth Offit; Ahmet Zehir; Michael F Walsh Journal: Nat Cancer Date: 2021-02-15