Genomic Analysis Made It Possible to Identify Gene-Driver Alterations Covering the Time Window between Diagnosis of Neuroblastoma 4S and the Progression to Stage 4.
Marzia OgnibenePatrizia De MarcoStefano ParodiMariaclaudia MeliAndrea Di CataldoFederico ZaraAnnalisa PezzoloPublished in: International journal of molecular sciences (2022)
Neuroblastoma (NB) is a tumor of the developing sympathetic nervous system. Despite recent advances in understanding the complexity of NB, the mechanisms that determine its regression or progression are still largely unknown. Stage 4S NB is characterized by a favorable course of disease and often by spontaneous regression, while progression to true stage 4 is a very rare event. Here, we focused on genomic analysis of an NB case that progressed from stage 4S to stage 4 with a very poor outcome. Array-comparative genomic hybridization (a-CGH) on tumor-tissue DNA, and whole-exome sequencing (WES) on exosomes DNA derived from plasma collected at the onset and at the tumor progression, pointed out relevant genetic changes that can explain this clinical worsening. The combination of a-CGH and WES data allowed for the identification iof somatic copy number aberrations and single-nucleotide variants in genes known to be responsible for aggressive NB. KLRB1 , MAPK3 and FANCA genes, which were lost at the time of progression, were studied for their possible role in this event by analyzing in silico the impact of their expression on the outcome of 786 NB patients.
Keyphrases
- copy number
- genome wide
- mitochondrial dna
- dna methylation
- poor prognosis
- single molecule
- end stage renal disease
- circulating tumor
- newly diagnosed
- ejection fraction
- bioinformatics analysis
- stem cells
- cell free
- mesenchymal stem cells
- prognostic factors
- long non coding rna
- electronic health record
- high throughput
- high resolution
- machine learning
- single cell
- nucleic acid
- circulating tumor cells
- big data
- transcription factor
- artificial intelligence
- patient reported outcomes
- molecular dynamics simulations