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

Cells

Angelica Zin¹  Carlo Zanon²  Claudia Pinato³  Eva Trevisson³  Sanja Aveic⁴  Gian Paolo Tonini⁴  Diana Corallo⁴  Marcella Pantile⁴  Ezequiel Monferrer⁵  Rosa Noguera⁵  Samuela Francescato⁶  Bartolomeo Rossi⁶  Alessandra Biffi⁶  Elisabetta Viscardi⁶  Salvador F. Aliño⁷  Maria Jose Herrero⁷ 

[1] Advanced Diagnostics and Target Discovery in Rare Pediatric Solid Tumors, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, C.so Stati Uniti 4, 35127 Padova, Italy;Bioinformatics Core Service, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, C.so Stati Uniti 4, 35127 Padova, Italy;Clinical Genetics Unit, Department of Woman’s and Child’s Health, University of Padova, Via Gustiniani 3, 35128 Padova, Italy;Laboratory of Target Discovery and Biology of Neuroblastoma, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, C.so Stati Uniti 4, 35127 Padova, Italy;Pathology Department, Medical School, University of Valencia-INCLIVA, 46010 Valencia, Spain;Pediatric Hematology, Oncology, and Stem Cell Transplant Center, Department of Woman’s and Child’s Health, University of Padova, Via Gustiniani 3, 35128 Padova, Italy;Pharmacogenetics Unit, Instituto Investigación Sanitaria La Fe and Department Pharmacology, University of Valencia, Avda. Fernando Abril Martorell 106, 46026 Valencia, Spain;

关键词: Neuroblastoma;    recurrent tumor;    array CGH;    clonal evolution;    whole exome sequencing;    3D tumoroids;   

DOI  :  10.3390/cells10102695

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown