Abstract 1021: Custom gene fusion assay for the rapid diagnosis of pediatric cancer in Sub-Saharan Africa
Authors: Gastier-Foster Julie M. , Hollingsworth E. Faith , Lopez-Terrada Dolores H. , Fisher Kevin E. , Roy Angshumoy , Wasswa Peter M. , Ozuah Nmazuo W. , Mehta Parth , Lubega Joseph , Allen Carl E. , Poplack David G. , Lutwama Fredrick 
Published: June 2022

The extreme disparity in pediatric cancer outcomes in low- and middle-income countries (LMICs, 20%) vs. the US (80%) can only be solved by addressing the inequities of access to high quality healthcare, including a precise diagnosis. In the US, excellent outcomes depend on treatments tailored to risk groups or specific characteristics of each child's cancer. Unfortunately, most pediatric cancer patients live in LMICs, where physicians often diagnose cancer based on clinical findings due to limited access to pathology and molecular genomic services. The goal of the Texas Children’s Hospital (TCH) Global HOPE program is to improve outcomes for pediatric cancer in Sub-Saharan Africa (SSA), and improved diagnostics is a key component. The aim of this study was to design and validate a cost-effective assay to improve pediatric cancer diagnoses in low resourced settings. The NanoString nCounter platform was chosen due to minimal technical expertise required, ability to test sub-optimal RNA, and rapid turn-around-time (2-3 days). Custom panels were designed to detect 439 specific breakpoints of gene fusions associated with pediatric hematologic malignancies and 436 with pediatric solid tumors. Validation was performed using &gt;140 samples with known fusion status. The NanoString results were consistent with a 99% accuracy after follow-up sequncing of any potential false negative/positive results (see table). Implementing this platform will greatly impact the ability to treat pediatric cancer in SSA by providing a more precise diagnosis. Testing will allow children to be treated according to the specific molecular characteristics of their cancers to maximize their chances of a cure, the same approach now considered standard-of-care in the United States. This work will also form the basis for establishing training in molecular and pediatric pathology in these LMICs, a critical need for long-term sustainability and reducing inequities of pediatric cancer care.

Custom Pediatric Cancer Fusion Panel Validation Custom Panel Unique Evaluable Samples Initial False Negatives Initial False Positives True False Negatives True False Positives Accuracy by NanoString Panles Heme 1 48 1 2 0 0 48 (100%) Heme 2 34 0 1 0 0 23 (100%) Heme 3 33 0 1 0 1 32 (97%) Heme 4 28 1 1 0 1 27 (96%) Total 143 2 5 0 2 141 (99%)

Citation Format: Julie M. Gastier-Foster, E. Faith Hollingsworth, Dolores H. Lopez-Terrada, Kevin E. Fisher, Angshumoy Roy, Peter M. Wasswa, Nmazuo W. Ozuah, Parth Mehta, Joseph Lubega, Carl E. Allen, David G. Poplack, Fredrick Lutwama. Custom gene fusion assay for the rapid diagnosis of pediatric cancer in Sub-Saharan Africa [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1021.