# Liquid biopsy approaches to inform neuroblastoma prognosis and disease monitoring > **NIH CA R37** · UNIVERSITY OF CHICAGO · 2026 · $622,186 ## Abstract Abstract Fewer than half of all children with high-risk neuroblastoma become long-term survivors. Currently, it is not possible to predict if a child will be cured with standard therapy or is destined to relapse. Furthermore, standard clinical evaluations lack sensitivity to detect minimal residual disease (MRD) that ultimately leads to recurrence. Thus, there is a critical challenge and an unmet need to develop new precision biomarkers to identify patients who will ultimately have a poor response to the high-intensity therapy and may benefit from alternate approaches. We will develop new biomarkers to guide treatment decisions using cell-free DNA (cfDNA) and a novel, epigenetic-based methodology that will identify underlying biology driving aggressive neuroblastoma. In many cancer types, analysis of cfDNA isolated from peripheral blood has shown promise, revealing biomarkers for diagnosis, prognostication, and tumor surveillance. Cytosines in DNA can either be unmodified, methylated (5- methylcytosine, 5mC), or contain an oxidized form of 5mC, 5-hydroxymethylcytosine (5hmC). Unlike 5mC, elevated 5hmC deposition across a gene body marks active transcription. In this proposal, we will use nano- hmC-seal, a whole-genome methodology for analyzing 5hmC modifications in cfDNA. Recently, we evaluated 5hmC in cfDNA collected serially from children with neuroblastoma and demonstrated that 5hmC profiles correlated with disease burden and patient outcome. Importantly, we also found a cfDNA 5hmC derived biomarker can distinguish patients with superior response to treatment from those at high risk for relapse. 5hmC profiles from cfDNA compared to diagnostic high-risk primary tumors demonstrated cfDNA is derived from clinically aggressive, malignant cells with activation of networks common in relapsed tumors. To prospectively determine the prognostic strength of 5hmC-based cfDNA biomarkers, we will use nano-hmC-seal to generate 5hmC profiles from clinically annotated serial bloo ## Key facts - **NIH application ID:** 11309677 - **Project number:** 5R37CA262781-05 - **Recipient organization:** UNIVERSITY OF CHICAGO - **Principal Investigator:** Mark Andrew Applebaum - **Activity code:** R37 (R01, R21, SBIR, etc.) - **Funding institute:** CA - **Fiscal year:** 2026 - **Award amount:** $622,186 - **Award type:** 5 - **Project period:** 2022-04-11T00:00:00 → 2027-03-31T00:00:00 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/11309677 ## Citation > US National Institutes of Health, RePORTER application 11309677, Liquid biopsy approaches to inform neuroblastoma prognosis and disease monitoring (5R37CA262781-05). Retrieved via AI Analytics 2026-07-13 from https://api.ai-analytics.org/grant/nih/11309677. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*