Grant Number:	1R01CA293366-01 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:	2024

Project Summary / Abstract Virtually fatal 60 years ago, pediatric cancers are now curable for 85% of children who have access to contemporary treatments and robust supportive care. However, for the 80% of children born in low and middle- income countries (LMIC), the picture is less promising. When viewed from a global perspective, only 30% of children in LMIC will survive their diagnosis of cancer, highlighting the stark contrast between high-income countries (HIC) and LMIC and representing one of the largest disparities in global health. While curable, cancers in children are not preventable. 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 in HIC, but unavailable for many LMIC treatment centers. 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 the global “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 LMIC. 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, St. Jude Children’s Research Hospital, and Indus Hospital and Healthcare Network in Pakistan to optimize technical and analytics methodologies for nanopore sequencing of challenging samples, specifically formalin-fixed, paraffin embedded specimens. We will harden existing protocols for deployment in LMIC 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 LMIC using a globally accessible platform.





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