Publications by authors named "Per Kogner"

Neuroblastoma (NB) is the most common extracranial childhood cancer, caused by the improper differentiation of developing trunk neural crest cells (tNCC) in the sympathetic nervous system. The N-methyladenosine (mA) epitranscriptomic modification controls post-transcriptional gene expression but the mechanism by which the mA methyltransferase complex METTL3/METTL14/WTAP is recruited to specific loci remains to be fully characterized. We explored whether the mA epitranscriptome could fine-tune gene regulation in migrating/differentiating tNCC.

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In this case report, we present the treatment outcomes of the first patient enrolled in the LuDO-N trial. The patient is a 21-month-old girl diagnosed with high-risk neuroblastoma (NB) and widespread skeletal metastasis. The patient initially underwent first-line therapy according to SIOPEN HRNBL-1 but was switched to second-line treatments due to disease progression, and she was finally screened for enrollment in the LuDO-N trial due to refractory disease.

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Article Synopsis
  • High-risk neuroblastoma has a dismal outlook, underscoring the need for innovative treatment strategies, particularly targeting Rho GTPase signaling which has been linked to both the disease and resistance to therapies.
  • The dual ROCK inhibitor RKI-1447 showed significant anti-cancer effects by reducing tumor growth, boosting cell death, and inhibiting key oncogenes like N-MYC in both lab and animal studies.
  • Combining RKI-1447 with BET inhibitors like ABBV-075 enhanced treatment effects and helped in overcoming resistance, presenting a potential strategy to improve neuroblastoma therapies while minimizing side effects.
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Background: Neuroblastoma (NB) is a complex disease, and the current understanding of NB biology is limited. Deregulation in genomic imprinting is a common event in malignancy. Since imprinted genes play crucial roles in early fetal growth and development, their role in NB pathogenesis could be suggested.

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Article Synopsis
  • - Neuroblastoma (NB) is a serious and complex childhood cancer that can vary widely in its progression; while some tumors may shrink on their own or respond to treatment, about 40% of patients face severe outcomes, especially those in the high-risk category.
  • - Researchers used advanced techniques, like single-cell multi-omics and sequencing, to study human NB and discovered not only adrenergic tumor cells but also unique, aneuploid SCP-like cells that exhibit clonal expansion and specific gene expression patterns.
  • - The study suggests that aneuploid SCP-like cells are a new aspect of NB, indicating that these cells, which may arise from the neural crest lineage, could play a key role in the early
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Unlabelled: Patients with anaplastic lymphoma kinase (ALK)-driven neuroblastoma may respond to tyrosine kinase inhibitors, but resistance to treatment occurs and methods currently used for detection of residual disease have limited sensitivity. Here, we present a national unselected cohort of five patients with relapsed or refractory ALK-driven neuroblastoma treated with lorlatinib as monotherapy and test the potential of targeted circulating tumor DNA (ctDNA) analysis as a guide for treatment decisions in these patients. We developed a sequencing panel for ultrasensitive detection of ALK mutations associated with neuroblastoma or resistance to tyrosine kinase inhibitors and used it for ctDNA analysis in 83 plasma samples collected longitudinally from the four patients who harbored somatic ALK mutations.

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Context: There is an increasing population of childhood cancer survivors (CCS) at risk for treatment-related toxicities, including skeletal morbidities. Bone mineral density (BMD) is a proxy for bone health and reductions are associated with osteoporosis and fractures.

Objective: To investigate bone health in CCS by conducting a systematic review and meta-analysis of BMD after completed treatments.

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Neuroblastoma (NB) is a heterogeneous childhood cancer with a slightly higher incidence in boys than girls, with the reason for this gender disparity unknown. Given the growing evidence for the involvement of loss of the Y chromosome (LoY) in male diseases including cancer, we investigated Y chromosome status in NB. Male NB tumor samples from a Swedish cohort, analyzed using Cytoscan HD SNP-microarray, were selected.

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Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by pathogenic variants in FBN1, with a hitherto unknown association with cancer. Here, we present two females with MFS who developed pediatric neuroblastoma. Patient 1 presented with neonatal MFS and developed an adrenal neuroblastoma with unfavorable tumor genetics at 10 months of age.

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Article Synopsis
  • The ChiCaP study investigates the role of childhood cancer predisposition (ChiCaP) syndromes and how integrating germline whole-genome sequencing (gWGS) with tumor sequencing can improve diagnosis and treatment strategies for children with solid tumors.
  • Out of 309 children tested, 11% were diagnosed with ChiCaP syndromes, often missed before, showing significant diagnostic yield especially in certain cancers like retinoblastomas and high-grade astrocytomas.
  • The findings underscore the importance of combining systematic phenotyping and genomic diagnostics, as it enables personalized care and tailored treatment recommendations for a substantial number of affected patients.
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  • Hearing loss affects 50-70% of children receiving cisplatin treatment, but a pediatric formula of intravenous sodium thiosulfate (STS) has been approved for its protection by major health agencies.
  • A review of 31 studies indicates that systemic STS can effectively reduce cisplatin-induced hearing loss (CIHL) in both children and adults, with its effectiveness depending on the timing and dosage of STS relative to cisplatin administration.
  • Although STS reduces CIHL, further research is necessary to better understand the pharmacokinetics of STS with cisplatin, its effects on patients with widespread disease, and its capability to stop the worsening of existing hearing loss.
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Neuroblastoma is a neural crest-derived tumor of the peripheral nervous system that is a leading cause of cancer-related deaths in children [...

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Neuroblastoma is an aggressive pediatric cancer with a high rate of metastasis to the BM. Despite intensive treatments including high-dose chemotherapy, the overall survival rate for children with metastatic neuroblastoma remains dismal. Understanding the cellular and molecular mechanisms of the metastatic tumor microenvironment is crucial for developing new therapies and improving clinical outcomes.

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Context: Recent preclinical studies reported that the BCL-2 inhibitor venetoclax can impair bone growth. A strategy to prevent such a side effect of this promising anticancer drug is highly desired. Earlier and studies suggested that the mitochondrial peptide humanin has the potential to prevent drug-induced growth impairment.

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Telomerase-negative tumors maintain telomere length by alternative lengthening of telomeres (ALT), but the underlying mechanism behind ALT remains poorly understood. A proportion of aggressive neuroblastoma (NB), particularly relapsed tumors, are positive for ALT (ALT+), suggesting that a better dissection of the ALT mechanism could lead to novel therapeutic opportunities. TERRA, a long non-coding RNA (lncRNA) derived from telomere ends, localizes to telomeres in a R-loop-dependent manner and plays a crucial role in telomere maintenance.

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Tumor cells are hallmarked by their capacity to undergo unlimited cell divisions, commonly accomplished either by mechanisms that activate or through the alternative lengthening of telomeres pathway. Neuroblastoma is a heterogeneous pediatric cancer, and the aim of this study was to characterize telomere maintenance mechanisms in a high-risk neuroblastoma cohort. All tumor samples were profiled with SNP microarrays and, when material was available, subjected to whole genome sequencing (WGS).

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Neuroblastoma is the most common extracranial solid tumor in childhood and arises from neural crest cells of the developing sympathetic nervous system. Prostaglandin E (PGE) has been identified as a key pro-inflammatory mediator of the tumor microenvironment (TME) that promotes neuroblastoma progression. We report that the interaction between the microRNA miR-574-5p and CUG-binding protein 1 (CUGBP1) induces the expression of microsomal prostaglandin E synthase 1 (mPGES-1) in neuroblastoma cells, which contributes to PGE biosynthesis.

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High-throughput drug screening enables the discovery of new anticancer drugs. Although monolayer cell cultures are commonly used for screening, their limited complexity and translational efficiency require alternative models. Three-dimensional cell cultures, such as multicellular tumor spheroids (MCTS), mimic tumor architecture and offer promising opportunities for drug discovery.

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Article Synopsis
  • The study examined how whole-genome sequencing (WGS) and RNA sequencing can help in diagnosing and treating childhood cancers, focusing on children with primary or relapsed solid tumors in Sweden.
  • Over the first 14 months, 118 tumors were analyzed, and 95% of those with mutations had clear clinical relevance, with significant findings such as additional subclassifications and potential treatment targets in 26% of the cases.
  • Overall, the research highlights the importance of integrating genomic data into clinical decision-making for improved diagnosis and treatment options in pediatric solid tumors.
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The Swedish Childhood Tumor Biobank (BTB) is a nonprofit national infrastructure for collecting tissue samples and genomic data from pediatric patients diagnosed with central nervous system (CNS) and other solid tumors. The BTB is built on a multidisciplinary network established to provide the scientific community with standardized biospecimens and genomic data, thereby improving knowledge of the biology, treatment and outcome of childhood tumors. As of 2022, over 1100 fresh-frozen tumor samples are available for researchers.

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Treatment-related skeletal complications are common in childhood cancer patients and survivors. Venetoclax is a BCL-2 inhibitor that has shown efficacy in hematological malignancies in adults and is being investigated in pediatric cancer clinical trials as a promising therapeutic modality. Venetoclax triggers cell death in cancer cells, but whether it exerts similar effects in normal bone cells, is unknown.

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Neuroblastoma (NB) is a childhood malignancy of the sympathetic nervous system. NB is mainly driven by copy number alterations, such as amplification, large deletions of chromosome arm 11q and gain of chromosome arm 17q, which are all markers of high‑risk disease. Genes targeted by recurrent, smaller, focal alterations include and .

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A preterm infant with central hypoventilation was diagnosed with multifocal neuroblastoma. Congenital anomalies of the autonomic nervous system in association with neuroblastoma are commonly associated with germline mutations in . Further, the gene is frequently mutated in both familial and sporadic neuroblastoma.

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Despite intensive therapy, children with high-risk neuroblastoma are at risk of treatment failure. We applied a multiomic system approach to evaluate metabolic vulnerabilities in human neuroblastoma. We combined metabolomics, CRISPR screening, and transcriptomic data across more than 700 solid tumor cell lines and identified dihydroorotate dehydrogenase (DHODH), a critical enzyme in pyrimidine synthesis, as a potential treatment target.

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