Germline mutations and new copy number variants among 40 pediatric cancer patients suspected for genetic predisposition

Gambale A;Russo R;Andolfo I;Quaglietta L;De Rosa G;Contestabile V;De Martino L;Genesio R;Pignataro P;Giglio S

Membro del Collaboration Group

;Capasso M;Parasole R;Pasini B;Iolascon A

2019-01-01

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Abstract

Cancer predisposition syndromes (CPS) result from germline pathogenic variants, and they are increasingly recognized in the etiology of many pediatric cancers. Herein, we report the genetic/genomic analysis of 40 pediatric patients enrolled from 2016 to 2018. Our diagnostic workflow was successful in 50% of screened cases. Overall, the proportion of CPS in our case series is 10.9% (20/184) of enrolled patients. Interestingly, 12.5% of patients achieved a conclusive diagnosis through the analysis of chromosomal imbalance. Indeed, we observed germline microdeletions/duplications of regions encompassing cancer-related genes in 50% of patients undergoing array-CGH: EIF3H duplication in a patient with infantile desmoplastic astrocytoma and low-grade Glioma; SLFN11 deletion, SOX4 duplication, and PARK2 partial deletion in three neuroblastoma patients; a PTPRD partial deletion in a child diagnosed with glioblastoma multiforme. Finally, we identified two cases due to DICER1 germline mutations.