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

Autores de INCLIVA

• 

  Ezequiel Monferrer Garzarán

  Autor

• 

  Rosa Noguera Salva

  Autor

Participantes ajenos a INCLIVA

• Corallo, Diana
• Zanon, Carlo
• Pantile, Marcella
• Tonini, Gian Paolo
• Zin, Angelica
• Francescato, Samuela
• Rossi, Bartolomeo
• Trevisson, Eva
• Pinato, Claudia
• Alino, Salvador F
• Herrero, Maria Jose
• Biffi, Alessandra
• Viscardi, Elisabetta
• Aveic, Sanja

Grupos y Plataformas de I+D+i

• Grupo de Investigación Translacional de Tumores Sólidos Pediátricos

  

  Leading Researcher

  Samuel Navarro Fos

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.

Keywords

• 3D tumoroids; Neuroblastoma; array CGH; clonal evolution; pharmacogenetics; recurrent tumor; single nucleotide variants; whole exome sequencing