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2.
PLoS One ; 17(8): e0273280, 2022.
Article in English | MEDLINE | ID: mdl-36037157

ABSTRACT

Neuroblastoma (NBL), one of the main death-causing cancers in children, is known for its remarkable genetic heterogeneity and varied patient outcome spanning from spontaneous regression to widespread disease. Specific copy number variations and single gene rearrangements have been proven to be associated with biological behavior and prognosis; however, there is still an unmet need to enlarge the existing armamentarium of prognostic and therapeutic targets. We performed whole exome sequencing (WES) of samples from 18 primary tumors and six relapse samples originating from 18 NBL patients. Our cohort consists of 16 high-risk, one intermediate, and one very low risk patient. The obtained results confirmed known mutational hotspots in ALK and revealed other non-synonymous variants of NBL-related genes (TP53, DMD, ROS, LMO3, PRUNE2, ERBB3, and PHOX2B) and of genes cardinal for other cancers (KRAS, PIK3CA, and FLT3). Beyond, GOSeq analysis determined genes involved in biological adhesion, neurological cell-cell adhesion, JNK cascade, and immune response of cell surface signaling pathways. We were able to identify novel coding variants present in more than one patient in nine biologically relevant genes for NBL, including TMEM14B, TTN, FLG, RHBG, SHROOM3, UTRN, HLA-DRB1, OR6C68, and XIRP2. Our results may provide novel information about genes and signaling pathways relevant for the pathogenesis and clinical course in high-risk NBL.


Subject(s)
DNA Copy Number Variations , Neuroblastoma , Child , Humans , Membrane Transport Proteins/genetics , Mutation , Neoplasm Recurrence, Local , Neuroblastoma/genetics , Neuroblastoma/metabolism , Exome Sequencing/methods
3.
J Gen Virol ; 93(Pt 10): 2310-2314, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22764320

ABSTRACT

An aquatic phage, designated F20, was characterized and its physico-chemical characteristics studied. F20 was specifically virulent to only two strains of Enterobacter aerogenes (ATCC 13048 and the multi-drug-resistant strain K113) among other species tested (n = 15). It was classified in the family Siphoviridae of T1-like viruses and contained a linear dsDNA genome estimated to be 51.5 kbp enclosed by an isometric capsid of 50±2 nm in diameter and a tail of 150±3 nm in length. F20 was able to survive in a broad pH range between 4 and 11, showed potential for future animal trials using oral solution and resisted chloroform and ethanol. It exhibited remarkable stability between room temperature and 70 °C for up to 150 min, and even up to 6 months at room temperature. Knowledge of this phage belonging to the widespread T1-like viruses might be helpful for adopting therapeutic strategies against E. aerogenes.


Subject(s)
Bacteriophages/genetics , Bacteriophages/isolation & purification , DNA, Viral/genetics , DNA/genetics , Enterobacter aerogenes/genetics , Genome, Viral , Amino Acid Sequence , Base Sequence , Genome, Viral/genetics , Molecular Sequence Data , Siphoviridae/genetics , Siphoviridae/isolation & purification , Temperature
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