Unraveling gene expression patterns in pediatric germ cell tumors: a nanopore sequencing approach

Abstract Germ cell tumors (GCTs) represent a rare but diverse spectrum of neoplasms originating from primordial germ cells and comprise 3.5% of tumor diagnoses among children. Recent advancements in molecular profiling have empowered researchers to probe the genetic landscape of GCTs, unveiling distinctive gene expression profiles across pediatric patients with GCTs utilizing diverse sequencing methodologies. In this study, we performed nanopore whole-transcriptome sequencing from 56 fresh-frozen and FFPE-preserved GCT samples, including 14 dysgerminomas, 13 yolk sac tumors, 11 mature teratomas, seven immature teratomas, eight mixed tumors, and three embryonal carcinomas. Despite shallow sequencing depth, nanopore sequencing provided robust signals and coverage in FFPE samples from these rare tumors. Principal component analysis of the resulting gene expression profiles showed clear differentiation between histological groups using a subset of genes identified from literature on GCTs. However, whole transcriptome analysis indicated that sample storage, in addition to histology, strongly impacts broad gene expression profile. This work shows that nanopore sequencing represents a potential globally accessible technology for characterization of pediatric germ cell tumors. Nanopore-based gene expression profiling of additional GCT samples representing broad and diverse tumor types will improve machine-learning-based GCT and broad solid tumor classification approaches. Biography Ana Peres is a PhD student at the Barretos Cancer Hospital in Brazil and also a visiting scholar at The University of North Carolina at Chapel Hill. Her current research in molecular oncology focuses on unraveling novel diagnostic tools for pediatric cancers, specifically on germ cell tumors.