Grant Number:	4R01CA293366-03 Interpret this number
Primary Investigator:	Wang, Jeremy
Organization:	Univ Of North Carolina Chapel Hill
Project Title:	Characterization of Diverse Pediatric Cancers in Lmic Using Low-Cost Nanopore Sequencing
Fiscal Year:	2026

Project Summary / Abstract Virtually fatal 60 years ago, pediatric cancers are now curable for 85% of children who have access to rapid, accurate diagnostics, contemporary treatments, and robust supportive care. However, there is commonly a diagnostic lag and corresponding increase in time-to-treatment, particularly critical for many acute pediatric cancers. The availability of gold standard molecular diagnostics – required to assign a treatment regimen personalized to a patient’s cancer – is limited to large tertiary, typically academic, cancer treatment centers. With no opportunities for prevention, but cost-effective malignancy-specific treatments increasingly available, an accurate diagnosis often represents the difference between potential survival and certain death. Modern methods to ascertain a correct diagnosis, such as flow-cytometry, cytogenetics, and molecular genomics, are standard of care, but unavailable in many primary and secondary cancer treatment centers, including the majority in rural areas. Transformative diagnostic approaches utilizing cost-effective, scalable technology are urgently needed. As genomic sequencing platforms become more accessible and analytical capabilities expand, integrating sequencing into childhood cancer diagnostics represents an opportunity to overcome this “pathology gap.” Classification of pediatric cancers using short-read RNA sequencing is established in research settings, but the capital and maintenance expenses of this approach are prohibitive for most settings. However, nanopore sequencing platforms require minimal capital investment and limited lab infrastructure, providing an opportunity for cost-effective, scalable molecular diagnostic technology in pediatric cancer treatment centers. We propose to establish and validate robust classification models for pediatric leukemias, extracranial solid tumors, and lymphomas using nanopore sequencing. We will leverage the close partnership between investigators at the University of North Carolina at Chapel Hill and St. Jude Children’s Research Hospital to optimize technical and analytics methodologies for nanopore sequencing of challenging samples, specifically formalin-fixed, paraffin embedded specimens. We will harden existing protocols for implementation and validation, and incorporate our analytic pipeline into integrated nanopore sequencing and base-calling hardware as a step toward affordable point-of-care cancer diagnostics for end users. Our objective is to develop and validate a cost-effective, sustainable, adaptable solution for the clinically relevant diagnosis and core genomic classification for childhood cancers in using a widely accessible platform.