Publications by authors named "Susanne Fransson"

Circulating tumor DNA (ctDNA) has shown potential as a non-invasive tumor biomarker in neuroblastoma. Previous studies used generic assays for detection of selected predefined oncogenic variants as markers of ctDNA, which limits the sensitivity and excludes a subset of patients from analysis. Here we assessed patient-specific ctDNA analysis for treatment evaluation and detection of relapse in neuroblastoma.

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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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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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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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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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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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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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Vesicoureteral reflux (VUR) is a common urological problem in children and its hereditary nature is well recognised. However, despite decades of research, the aetiological factors are poorly understood and the genetic background has been elucidated in only a minority of cases. To explore the molecular aetiology of primary hereditary VUR, we performed whole-exome sequencing in 13 large families with at least three affected cases.

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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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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 of neuroblastoma patients showing amplification of one or multiple 12q loci was identified.

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Background: Transgenic animal models are crucial for the study of gene function and disease, and are widely utilized in basic biological research, agriculture and pharma industries. Since the current methods for generating transgenic animals result in the random integration of the transgene under study, the phenotype may be compromised due to disruption of known genes or regulatory regions. Unfortunately, most of the tools that predict transgene insertion sites from high-throughput data are not publicly available or not properly maintained.

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Vesicoureteral reflux (VUR) is a congenital malformation carrying a high risk of recurrent urinary tract infections (UTI) and, at worst, chronic renal failure. Familial clustering implies a genetic etiology, but studies during the past few decades have demonstrated a causal gene variant in <10% of patients with VUR. The aim of the present study was to search for fully or partially shared ancestral haplotypes in 14 families from south-western Sweden with at least three affected members.

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Childhood medulloblastoma and high-risk neuroblastoma frequently present with segmental gain of chromosome 17q corresponding to aggressive tumors and poor patient prognosis. Located within the 17q-gained chromosomal segments is at chromosome 17q23.2.

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is a negative regulator of p53 and genomic aberrations resulting in increased activity of have been observed in cancers of different origins, indicating that has oncogenic properties. We established a transgenic mouse model overexpressing and showed that these mice developed a wide variety of cancers. -expressing mice developed tumors phenotypically and genetically similar to tumors in mice with dysfunctional p53.

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High-risk neuroblastoma (NB) is responsible for a disproportionate number of childhood deaths due to cancer. One indicator of high-risk NB is amplification of the neural MYC (MYCN) oncogene, which is currently therapeutically intractable. Identification of anaplastic lymphoma kinase (ALK) as an NB oncogene raised the possibility of using ALK tyrosine kinase inhibitors (TKIs) in treatment of patients with activating ALK mutations.

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Neuroblastoma is the most common and deadly childhood tumor. Relapsed or refractory neuroblastoma has a very poor prognosis despite recent treatment advances. To investigate genomic alterations associated with relapse and therapy resistance, whole-genome sequencing was performed on diagnostic and relapsed lesions together with constitutional DNA from seven children.

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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 an important role for oncogenic ALK-ERK1/2-SP1 signaling in the maintenance of undifferentiated neural crest-derived progenitors through the repression of DLG2, a candidate tumor suppressor gene in neuroblastoma.

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Intestinal degenerative neuropathy without extra-intestinal involvement occurs as familial forms (FIDN) but the genetics behind is unknown. We studied a Swedish family with autosomal dominant disease and several cases of chronic intestinal pseudo-obstruction (CIP). We included 33 members of a family sharing a male ancestor.

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Gain of chromosome arm 2p is a previously described entity in neuroblastoma (NB). This genomic address is home to two important oncogenes in NB-MYCN and anaplastic lymphoma kinase (ALK). MYCN amplification is a critical prognostic factor coupled with poor prognosis in NB.

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