Integrated CGH/WES Analyses Advance Understanding of Aggressive Neuroblastoma Evolution: A Case Study
Diana Corallo,
Carlo Zanon,
Marcella Pantile,
Gian Paolo Tonini,
Angelica Zin,
Samuela Francescato,
Bartolomeo Rossi,
Eva Trevisson,
Claudia Pinato,
Ezequiel Monferrer,
Rosa Noguera,
Salvador F. Aliño,
Maria Jose Herrero,
Alessandra Biffi,
Elisabetta Viscardi,
Sanja Aveic
Affiliations
Diana Corallo
Laboratory of Target Discovery and Biology of Neuroblastoma, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, C.so Stati Uniti 4, 35127 Padova, Italy
Carlo Zanon
Bioinformatics Core Service, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, C.so Stati Uniti 4, 35127 Padova, Italy
Marcella Pantile
Laboratory of Target Discovery and Biology of Neuroblastoma, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, C.so Stati Uniti 4, 35127 Padova, Italy
Gian Paolo Tonini
Laboratory of Target Discovery and Biology of Neuroblastoma, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, C.so Stati Uniti 4, 35127 Padova, Italy
Angelica Zin
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
Samuela Francescato
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
Bartolomeo Rossi
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
Eva Trevisson
Clinical Genetics Unit, Department of Woman’s and Child’s Health, University of Padova, Via Gustiniani 3, 35128 Padova, Italy
Claudia Pinato
Clinical Genetics Unit, Department of Woman’s and Child’s Health, University of Padova, Via Gustiniani 3, 35128 Padova, Italy
Ezequiel Monferrer
Pathology Department, Medical School, University of Valencia-INCLIVA, 46010 Valencia, Spain
Rosa Noguera
Pathology Department, Medical School, University of Valencia-INCLIVA, 46010 Valencia, Spain
Salvador F. Aliño
Pharmacogenetics Unit, Instituto Investigación Sanitaria La Fe and Department Pharmacology, University of Valencia, Avda. Fernando Abril Martorell 106, 46026 Valencia, Spain
Maria Jose Herrero
Pharmacogenetics Unit, Instituto Investigación Sanitaria La Fe and Department Pharmacology, University of Valencia, Avda. Fernando Abril Martorell 106, 46026 Valencia, Spain
Alessandra Biffi
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
Elisabetta Viscardi
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
Sanja Aveic
Laboratory of Target Discovery and Biology of Neuroblastoma, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, C.so Stati Uniti 4, 35127 Padova, Italy
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.
