A5085833100- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Cancer therapeutics and mechanisms
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- RNA modifications and cancer
- Neurofibromatosis and Schwannoma Cases
- Pediatric Urology and Nephrology Studies
- Cell death mechanisms and regulation
- Cancer-related molecular mechanisms research
- Fetal and Pediatric Neurological Disorders
- Renal and related cancers
- Urological Disorders and Treatments
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Virus-based gene therapy research
- Retinopathy of Prematurity Studies
- Ubiquitin and proteasome pathways
- Lung Cancer Treatments and Mutations
- Cancer-related gene regulation
- Adrenal and Paraganglionic Tumors
- Neonatal Respiratory Health Research
- Testicular diseases and treatments
- Childhood Cancer Survivors' Quality of Life
- Genetics and Neurodevelopmental Disorders
University of Gothenburg
2016-2025
Sahlgrenska University Hospital
2011-2019
Université Paris Cité
2014
Purpose In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated potential role of mutations in neuroblastoma clonal evolution. Methods analyzed 54 paired diagnosis–relapse samples using Sanger sequencing. When an mutation was observed one sample, a minor mutated component other sample searched for more than 100,000× deep sequencing relevant hotspot, with sensitivity 0.17%. Results All nine ALK-mutated cases at diagnosis demonstrated same relapse,...
Abstract Telomerase-negative tumors maintain telomere length by alternative lengthening of telomeres (ALT), but the underlying mechanism behind ALT remains poorly understood. A proportion aggressive neuroblastoma (NB), particularly relapsed tumors, are positive for (ALT+), suggesting that a better dissection could lead to novel therapeutic opportunities. TERRA, long non-coding RNA (lncRNA) derived from ends, localizes in R-loop-dependent manner and plays crucial role maintenance. Here we...
Abstract Background Hypermethylation of promotor CpG islands is a common mechanism that inactivates tumor suppressor genes in cancer. Genes belonging to the RASSF gene family have frequently been reported as epigenetically silenced by methylation human cancers. Two members this family, RASSF1A and RASSF5A methylated neuroblastoma. Data from our previously performed genome-wide DNA array analysis indicated other are targeted Results In current study, we found several ( RASSF2 , RASSF4 RASSF5...
Epigenetic mechanisms such as DNA methylation and histone modifications are important regulators of gene expression frequently involved in silencing tumor suppressor genes. In order to identify genes that epigenetically regulated neuroblastoma tumors, we treated four cell lines with the demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-dC) either separately or conjunction deacetylase inhibitor trichostatin A (TSA). Expression was analyzed using whole-genome arrays activated by treatment....
MEK inhibitors induce feedback AKT-mTORC2–mediated survival signaling in ALK-addicted neuroblastoma cells.
High-risk neuroblastomas typically display an undifferentiated or poorly differentiated morphology. It is therefore vital to understand molecular mechanisms that block the differentiation process. We identify important role for oncogenic ALK-ERK1/2-SP1 signaling in maintenance of neural crest-derived progenitors through repression DLG2, a candidate tumor suppressor gene neuroblastoma. DLG2 expressed murine "bridge signature" represents transcriptional transition state when crest cells...
<title>Abstract</title> Purpose Segmental gain of chromosome 17q is the most common genetic aberration in high-risk neuroblastoma, but its role disease progression poorly understood. This study aims to address contribution neuroblastoma malignancy. Patients and methods: We analyzed transcriptional landscape 417 patients across various risk groups clinical stages using multi-omic approaches. Single-cell RNA/DNA sequencing SNP arrays were combined characterize genomic aberrations, while...
Anaplastic lymphoma kinase (ALK) has been demonstrated to be deregulated in sporadic as well familiar cases of neuroblastoma (NB). Whereas ALK‐fusion proteins are common and lung cancer, there few reports ALK rearrangements NB indicating that mainly exerts its oncogenic capacity via activating mutations and/or overexpression this tumor type. In study, 332 tumors 13 cell lines were screened by high resolution single nucleotide polymorphism microarray. Gain 2p was detected 23% (60/332) primary...
Genetic analysis in neuroblastoma has identified the profound influence of MYCN amplification and 11q deletion patients' prognosis. These two features high-risk usually occur as mutually exclusive genetic markers, although rare cases both are present same tumor. The purpose this study was to characterize profile these uncommon neuroblastomas harboring features.We selected 18 with MNA plus loss detected by FISH. Chromosomal aberrations were analyzed using Multiplex Ligation-dependent Probe...
Abstract In neuroblastoma, MYCN amplification and 11q-deletion are important, although incomplete, markers of high-risk disease. It is therefore relevant to characterize additional alterations that can function as prognostic and/or predictive markers. Using SNP-microarrays, a group neuroblastoma patients showing one or multiple 12q loci was identified. Two containing CDK4 MDM2 were commonly co-amplified, either locus in the absence other observed. Pharmacological inhibition CDK4/6 with...
ABSTRACT Neuroblastoma (NB) is a heterogeneous childhood cancer with slightly higher incidence in boys than girls, the reason for this gender disparity unknown. Given growing evidence involvement of loss Y chromosome (LoY) male diseases including cancer, we investigated status NB. Male NB tumor samples from Swedish cohort, analyzed using Cytoscan HD SNP‐microarray, were selected. Seventy tumors aneuploidy chromosome, and these data correlated other genetic, biological, clinical parameters....
Gain of chromosome arm 2p is a previously described entity in neuroblastoma (NB). This genomic address home to two important oncogenes NB-MYCN and anaplastic lymphoma kinase (ALK). MYCN amplification critical prognostic factor coupled with poor prognosis NB. Mutation the ALK receptor tyrosine has been both somatic familial Here, activation occurs context full-length receptor, exemplified by activating point mutations overexpression activation, absence genetic mutation also In addition,...
In the pediatric cancer neuroblastoma, analysis of recurrent chromosomal aberrations such as loss chromosome 1p, 11q, gain 17q and MYCN amplification are used for patient stratification subsequent therapy decision making. Different techniques have been detection segmental abnormalities, including fluorescence in situ hybridization (FISH), comparative genomic (CGH)-microarrays multiplex ligation-dependent probe (MLPA). However, next-generation sequencing becomes available clinical use, this...
Neuroblastoma (NB) is a childhood malignancy of the sympathetic nervous system. NB mainly driven by copy number alterations, such as <em>MYCN</em> amplification, large deletions chromosome arm 11q and gain 17q, which are all markers high‑risk disease. Genes targeted recurrent, smaller, focal alterations include <em>CDKN2A/B, TERT, PTPRD</em> <em>ATRX</em>. Our previous study on relapsed detected recurrent structural centered at limbic system‑associated membrane protein (<em>LSAMP</em>; HUGO...
Abstract Patients with anaplastic lymphoma kinase (ALK)–driven neuroblastoma may respond to tyrosine inhibitors, but resistance treatment occurs and methods currently used for detection of residual disease have limited sensitivity. Here, we present a national unselected cohort five patients relapsed or refractory ALK-driven treated lorlatinib as monotherapy test the potential targeted circulating tumor DNA (ctDNA) analysis guide decisions in these patients. We developed sequencing panel...
Abstract The ALK tyrosine kinase receptor is oncogenically activated in neuroblastoma. Whereas numerous fusion genes have been reported different malignancies, neuroblastoma mainly through point mutations. Three hotspot residues (F1174, F1245, and R1275) account for 85% of mutant seen In a cohort 105 Swedish cases all stages, these regions were re-sequenced (>5000X). mutations detected 16 patients (range variant allele fraction: 2.7–60%). Mutations at the F1174 F1245 observed eleven three...
In this case report, we present the treatment outcomes of first patient enrolled in LuDO-N trial. The is a 21-month-old girl diagnosed with high-risk neuroblastoma (NB) and widespread skeletal metastasis. initially underwent first-line therapy according to SIOPEN HRNBL-1 but was switched second-line treatments due disease progression, she finally screened for enrollment trial refractory disease. Upon enrollment, received two rounds radiolabeled somatostatin analogue lutetium-177 octreotate (
<p>Supplementary figures 1-4, supplementary tables and case information</p>
Tumor cells are hallmarked by their capacity to undergo unlimited cell divisions, commonly accomplished either mechanisms that activate