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[Preprint]. 2025 Jul 17:2025.07.16.25331652. [Version 1] doi: 10.1101/2025.07.16.25331652

Confounding factors affecting analysis of germline structural variants in pediatric solid tumors

Pandurang Kolekar, Rebecca S Kaufman, Nadezhda V Terekhanova, Jinghui Zhang, John M Maris, Sharon J Diskin, Xiaotu Ma
PMCID: PMC12338921  PMID: 40791691

Abstract

We provide data showing the germline predisposition structural variants (SV) involving MYCN and RAF1::TMEM40 reported by Gillani et al. (2025) in pediatric solid tumors are confounded by circulating tumor DNA (ctDNA) and enrichment for Hispanic or Latino ancestry, respectively. We suggest that future germline studies should ensure analyses of tumor-in-normal contamination for non-polymorphic markers and careful examination of population stratification for polymorphic markers to ensure clinical relevance.

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