American Association for Cancer Research
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10780432ccr181345-sup-201077_2_supp_4967166_pd1qg9.xlsx (15.95 kB)

Supplementary table 2 from Clinically Relevant and Minimally Invasive Tumor Surveillance of Pediatric Diffuse Midline Gliomas Using Patient-Derived Liquid Biopsy

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posted on 2023-03-31, 20:47 authored by Eshini Panditharatna, Lindsay B. Kilburn, Mariam S. Aboian, Madhuri Kambhampati, Heather Gordish-Dressman, Suresh N. Magge, Nalin Gupta, John S. Myseros, Eugene I. Hwang, Cassie Kline, John R. Crawford, Katherine E. Warren, Soonmee Cha, Winnie S. Liang, Michael E. Berens, Roger J. Packer, Adam C. Resnick, Michael Prados, Sabine Mueller, Javad Nazarian

Midline glioma patient demographic information, and samples analyzed for genomic and ctDNA studies.

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Clinical and Translational Science Institute at Children's National

National Center for Advancing Translational Sciences

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ARTICLE ABSTRACT

Pediatric diffuse midline glioma (DMG) are highly malignant tumors with poor clinical outcomes. Over 70% of patients with DMG harbor the histone 3 p.K27M (H3K27M) mutation, which correlates with a poorer clinical outcome, and is also used as a criterion for enrollment in clinical trials. Because complete surgical resection of DMG is not an option, biopsy at presentation is feasible, but rebiopsy at time of progression is rare. While imaging and clinical-based disease monitoring is the standard of care, molecular-based longitudinal characterization of these tumors is almost nonexistent. To overcome these hurdles, we examined whether liquid biopsy allows measurement of disease response to precision therapy. We established a sensitive and specific methodology that detects major driver mutations associated with pediatric DMGs using droplet digital PCR (n = 48 subjects, n = 110 specimens). Quantification of circulating tumor DNA (ctDNA) for H3K27M was used for longitudinal assessment of disease response compared with centrally reviewed MRI data. H3K27M was identified in cerebrospinal fluid (CSF) and plasma in 88% of patients with DMG, with CSF being the most enriched for ctDNA. We demonstrated the feasibility of multiplexing for detection of H3K27M, and additional driver mutations in patient's tumor and matched CSF, maximizing the utility of a single source of liquid biome. A significant decrease in H3K27M plasma ctDNA agreed with MRI assessment of tumor response to radiotherapy in 83% (10/12) of patients. Our liquid biopsy approach provides a molecularly based tool for tumor characterization, and is the first to indicate clinical utility of ctDNA for longitudinal surveillance of DMGs.

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