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Retrospective Evaluation of Somatic Alterations in Cell-Free DNA from Blood in Retinoblastoma

PURPOSE: Analysis of circulating tumor DNA (ctDNA) in the plasma of patients with retinoblastoma and simulating lesions. DESIGN: Retrospective cross-sectional study of the association of plasma ctDNA from retinoblastoma and simulating lesions with disease course. PARTICIPANTS: Fifty-eight Memorial S...

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Autores principales: Abramson, David H., Mandelker, Diana, Francis, Jasmine H., Dunkel, Ira J., Brannon, A. Rose, Benayed, Ryma, Berger, Michael F., Arcila, Maria E., Ladanyi, Marc, Friedman, Danielle Novetsky, Jayakumaran, Gowtham, Diosdado, Monica S., Robbins, Melissa A., Haggag-Lindgren, Dianna, Shukla, Neerav, Walsh, Michael, Kothari, Prachi, Tsui, Dana W.Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560572/
https://www.ncbi.nlm.nih.gov/pubmed/36246006
http://dx.doi.org/10.1016/j.xops.2021.100015
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author Abramson, David H.
Mandelker, Diana
Francis, Jasmine H.
Dunkel, Ira J.
Brannon, A. Rose
Benayed, Ryma
Berger, Michael F.
Arcila, Maria E.
Ladanyi, Marc
Friedman, Danielle Novetsky
Jayakumaran, Gowtham
Diosdado, Monica S.
Robbins, Melissa A.
Haggag-Lindgren, Dianna
Shukla, Neerav
Walsh, Michael
Kothari, Prachi
Tsui, Dana W.Y.
author_facet Abramson, David H.
Mandelker, Diana
Francis, Jasmine H.
Dunkel, Ira J.
Brannon, A. Rose
Benayed, Ryma
Berger, Michael F.
Arcila, Maria E.
Ladanyi, Marc
Friedman, Danielle Novetsky
Jayakumaran, Gowtham
Diosdado, Monica S.
Robbins, Melissa A.
Haggag-Lindgren, Dianna
Shukla, Neerav
Walsh, Michael
Kothari, Prachi
Tsui, Dana W.Y.
author_sort Abramson, David H.
collection PubMed
description PURPOSE: Analysis of circulating tumor DNA (ctDNA) in the plasma of patients with retinoblastoma and simulating lesions. DESIGN: Retrospective cross-sectional study of the association of plasma ctDNA from retinoblastoma and simulating lesions with disease course. PARTICIPANTS: Fifty-eight Memorial Sloan Kettering Cancer Center patients with retinoblastoma comprising 68 plasma ctDNA samples and 5 with retinoblastoma-simulating lesions. METHODS: The ctDNA analyzed with hybridization capture and next-generation sequencing in blood (plasma) of patients who had retinoblastoma or simulating lesions were evaluated for association with clinical course of the disease. MAIN OUTCOME MEASURES: Presence or absence of molecular aberrations in the RB1 gene and correlations with clinical features. RESULTS: RB1 cell-free DNA (cfDNA) was detected in 16 of 19 patients with newly diagnosed, untreated intraocular retinoblastoma and in 3 of 3 patients with newly diagnosed, untreated metastatic disease. It was also present in 3 patients with recurrent intraocular disease before therapy, but was not present in patients with recurrent disease who received intra-arterial chemotherapy, nor in 21 patients who had undergone enucleation for unilateral disease. In 1 patient who had delayed treatment (insurance reasons) and showed rapid growth of the intraocular tumor, the variant allele frequency increased in 1 month from 0.34% to 2.48%. No RB1 mutations were detected in the cfDNA from plasma of patients with simulating lesions (3 with Coats disease and 1 with persistent fetal vasculature [PFV]). In 2 patients, we identified 2 independent RB1 mutations in plasma. CONCLUSIONS: Mutations in RB1 were found in the cfDNA from blood of patients with newly diagnosed, untreated retinoblastoma and in patients who showed disease recurrence in the eye after prior treatment, but not in unilateral retinoblastoma after enucleation Levels of ctDNA increase in patients with progressive disease who did not receive any treatment. High plasma cfDNA levels were detected in patients with newly diagnosed metastatic disease, and these levels decreased after systemic chemotherapy was administered. Further validation is needed for measuring the somatic alterations in cfDNA from blood in retinoblastoma that could provide a promising method of monitoring patients in the future.
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spelling pubmed-95605722022-10-14 Retrospective Evaluation of Somatic Alterations in Cell-Free DNA from Blood in Retinoblastoma Abramson, David H. Mandelker, Diana Francis, Jasmine H. Dunkel, Ira J. Brannon, A. Rose Benayed, Ryma Berger, Michael F. Arcila, Maria E. Ladanyi, Marc Friedman, Danielle Novetsky Jayakumaran, Gowtham Diosdado, Monica S. Robbins, Melissa A. Haggag-Lindgren, Dianna Shukla, Neerav Walsh, Michael Kothari, Prachi Tsui, Dana W.Y. Ophthalmol Sci Original Article PURPOSE: Analysis of circulating tumor DNA (ctDNA) in the plasma of patients with retinoblastoma and simulating lesions. DESIGN: Retrospective cross-sectional study of the association of plasma ctDNA from retinoblastoma and simulating lesions with disease course. PARTICIPANTS: Fifty-eight Memorial Sloan Kettering Cancer Center patients with retinoblastoma comprising 68 plasma ctDNA samples and 5 with retinoblastoma-simulating lesions. METHODS: The ctDNA analyzed with hybridization capture and next-generation sequencing in blood (plasma) of patients who had retinoblastoma or simulating lesions were evaluated for association with clinical course of the disease. MAIN OUTCOME MEASURES: Presence or absence of molecular aberrations in the RB1 gene and correlations with clinical features. RESULTS: RB1 cell-free DNA (cfDNA) was detected in 16 of 19 patients with newly diagnosed, untreated intraocular retinoblastoma and in 3 of 3 patients with newly diagnosed, untreated metastatic disease. It was also present in 3 patients with recurrent intraocular disease before therapy, but was not present in patients with recurrent disease who received intra-arterial chemotherapy, nor in 21 patients who had undergone enucleation for unilateral disease. In 1 patient who had delayed treatment (insurance reasons) and showed rapid growth of the intraocular tumor, the variant allele frequency increased in 1 month from 0.34% to 2.48%. No RB1 mutations were detected in the cfDNA from plasma of patients with simulating lesions (3 with Coats disease and 1 with persistent fetal vasculature [PFV]). In 2 patients, we identified 2 independent RB1 mutations in plasma. CONCLUSIONS: Mutations in RB1 were found in the cfDNA from blood of patients with newly diagnosed, untreated retinoblastoma and in patients who showed disease recurrence in the eye after prior treatment, but not in unilateral retinoblastoma after enucleation Levels of ctDNA increase in patients with progressive disease who did not receive any treatment. High plasma cfDNA levels were detected in patients with newly diagnosed metastatic disease, and these levels decreased after systemic chemotherapy was administered. Further validation is needed for measuring the somatic alterations in cfDNA from blood in retinoblastoma that could provide a promising method of monitoring patients in the future. Elsevier 2021-03-16 /pmc/articles/PMC9560572/ /pubmed/36246006 http://dx.doi.org/10.1016/j.xops.2021.100015 Text en © 2021 by the American Academy of Ophthalmology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Abramson, David H.
Mandelker, Diana
Francis, Jasmine H.
Dunkel, Ira J.
Brannon, A. Rose
Benayed, Ryma
Berger, Michael F.
Arcila, Maria E.
Ladanyi, Marc
Friedman, Danielle Novetsky
Jayakumaran, Gowtham
Diosdado, Monica S.
Robbins, Melissa A.
Haggag-Lindgren, Dianna
Shukla, Neerav
Walsh, Michael
Kothari, Prachi
Tsui, Dana W.Y.
Retrospective Evaluation of Somatic Alterations in Cell-Free DNA from Blood in Retinoblastoma
title Retrospective Evaluation of Somatic Alterations in Cell-Free DNA from Blood in Retinoblastoma
title_full Retrospective Evaluation of Somatic Alterations in Cell-Free DNA from Blood in Retinoblastoma
title_fullStr Retrospective Evaluation of Somatic Alterations in Cell-Free DNA from Blood in Retinoblastoma
title_full_unstemmed Retrospective Evaluation of Somatic Alterations in Cell-Free DNA from Blood in Retinoblastoma
title_short Retrospective Evaluation of Somatic Alterations in Cell-Free DNA from Blood in Retinoblastoma
title_sort retrospective evaluation of somatic alterations in cell-free dna from blood in retinoblastoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560572/
https://www.ncbi.nlm.nih.gov/pubmed/36246006
http://dx.doi.org/10.1016/j.xops.2021.100015
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