Integrated CGH/WES Analyses Advance Understanding of Aggressive Neuroblastoma Evolution: A Case Study

Abstract

Neuroblastoma (NB) is the most common extra-cranial malignancy in preschool children. To portray the genetic landscape of an overly aggressive NB leading to a rapid clinical progression of the disease, tumor DNA collected pre- and post-treatment has been analyzed. Array comparative genomic hybridization (aCGH), whole-exome sequencing (WES), and pharmacogenetics approaches, respectively, have identified relevant copy number alterations (CNAs), single nucleotide variants (SNVs), and polymorphisms (SNPs) that were then combined into an integrated analysis. Spontaneously formed 3D tumoroids obtained from the recurrent mass have also been characterized. The results prove the power of combining CNAs, SNVs, and SNPs analyses to assess clonal evolution during the disease progression by evidencing multiple clones at disease onset and dynamic genomic alterations during therapy administration. The proposed molecular and cytogenetic integrated analysis empowers the disease follow-up and the prediction of tumor recurrence.

Recurrent human 16p11.2 microdeletions in type I Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome patients in Chinese Han population

“…To our best knowledge, this is the first CNVs analysis performed in Chinese MRKH syndrome based on aCGH. Despite a lot of algorithms have been developed to detect CNVs from sequencing data, high resolution version of aCGH is still an appropriate methodology for the analysis of chromosome aberrations in a cohort (Corallo et al, 2021; Retterer et al, 2015). The application of whole‐exome sequencing (WES) surely reduced related costs of sequencing while there is also deficiency considering the restricted detection in exomic space and the data processing itself (Rapti et al, 2022).…”