Predisposition footprints in the somatic genome of Wilms tumours.

Ten percent of children with cancer harbour a mutation in a predisposition gene. In children with the kidney cancer, Wilms tumour, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumourigenesis.

Characteristics and outcome of synchronous bilateral Wilms tumour in the SIOP WT 2001 Study: Report from the SIOP Renal Tumour Study Group (SIOP-RTSG).

Background: Among patients with nephroblastoma, those with bilateral disease are a unique population where maximising tumour control must be balanced with preserving renal parenchyma.

Methods: The SIOP 2001 protocol recommended surgery after neoadjuvant cycle(s) of Dactinomycin and Vincristine (AV) with response-adapted intensification, if needed. Adjuvant treatment was given based on the lesion with the worst histology.

The impact of the route to diagnosis in nephroblastoma.

Introduction: Wilms tumor (WT) is the most common childhood kidney cancer. It is a rapid growing embryonal tumor in young children and can be diagnosed with and without tumor related symptoms.

Methods: We retrospectively analyzed the route to diagnosis of WT treated prospectively according to the SIOP 93-01/GPOH and 2001/GPOH in Germany between 1993 and 2022.

TRIM28 inactivation in epithelial nephroblastoma is frequent and often associated with predisposing TRIM28 germline variants.

Wilms tumors (WTs) are histologically diverse childhood cancers with variable contributions of blastema, stroma, and epithelia. A variety of cancer genes operate in WTs, including the tripartite-motif-containing-28 gene (TRIM28). Case reports and small case series suggest that TRIM28 mutations are associated with epithelial morphology and WT predisposition.

Tumor biology, biomarkers, and liquid biopsy in pediatric renal tumors.

The expansion of knowledge regarding driver mutations for Wilms tumor (WT) and malignant rhabdoid tumor of the kidney (MRT) and various translocations for other pediatric renal tumors opens up new possibilities for diagnosis and treatment. In addition, there are growing data surrounding prognostic factors that can be used to stratify WT treatment to improve outcomes. Here, we review the molecular landscape of WT and other pediatric renal tumors as well as WT prognostic factors.

The genomic landscape of pediatric renal cell carcinomas.

Pediatric renal cell carcinomas (RCC) differ from their adult counterparts not only in histologic subtypes but also in clinical characteristics and outcome. However, the underlying biology is still largely unclear. For this reason, we performed whole-exome and transcriptome sequencing analyses on a cohort of 25 pediatric RCC patients with various histologic subtypes, including 10 MiT family translocation (MiT) and 10 papillary RCCs.

The DGCR8 E518K mutation found in Wilms tumors leads to a partial miRNA processing defect that alters gene expression patterns and biological processes.

Wilms tumor (WT) is the most common renal tumor in childhood. We and others have previously identified oncogenic driver mutations affecting the microprocessor genes DROSHA and DGCR8 that lead to altered miRNA expression patterns. In the case of DGCR8, a single recurrent hotspot mutation (E518K) was found in the RNA binding domain.

Correction: Welter et al. Characteristics of Nephroblastoma/Nephroblastomatosis in Children with a Clinically Reported Underlying Malformation or Cancer Predisposition Syndrome. 2021, , 5016.

In the original article [...

MYCN and MAX alterations in Wilms tumor and identification of novel N-MYC interaction partners as biomarker candidates.

Background: Wilms tumor (WT) is the most common renal tumor in childhood. Among others, MYCN copy number gain and MYCN P44L and MAX R60Q mutations have been identified in WT. MYCN encodes a transcription factor that requires dimerization with MAX to activate transcription of numerous target genes.

Wilms tumour.

Wilms tumour (WT) is a childhood embryonal tumour that is paradigmatic of the intersection between disrupted organogenesis and tumorigenesis. Many WT genes play a critical (non-redundant) role in early nephrogenesis. Improving patient outcomes requires advances in understanding and targeting of the multiple genes and cellular control pathways now identified as active in WT development.

Characteristics of Nephroblastoma/Nephroblastomatosis in Children with a Clinically Reported Underlying Malformation or Cancer Predisposition Syndrome.

(1) Background: about 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. (2) Methods: this retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies.

[CME/Answers: Mushroom Poisoning in the Family Practice].

CME/Answers: Mushroom Poisoning in the Family Practice In the general medical practice, it is not trivial to distinguish between banal intolerances after consumption of edible mushrooms and the initial symptoms of poisoning with potentially fatal outcome. Nevertheless, there are some criteria that can be used as clinical guidance: A latency of six hours or more between the consumption of gilled mushrooms that have not been checked by experts and the onset of mostly severe vomiting and diarrhea is indicative of poisoning with amatoxins, the toxins i.e.

[CME: Mushroom Poisoning in the Family Practice].

CME: Mushroom Poisoning in the Family Practice In the general medical practice, it is not trivial to distinguish between banal intolerances after consumption of edible mushrooms and the initial symptoms of poisoning with potentially fatal outcome. Nevertheless, there are some criteria that can be used as clinical guidance: A latency of six hours or more between the consumption of gilled mushrooms that have not been checked by experts and the onset of mostly severe vomiting and diarrhea is indicative of poisoning with amatoxins, the toxins i.e.

HEYL Regulates Neoangiogenesis Through Overexpression in Both Breast Tumor Epithelium and Endothelium.

Blocking tumor angiogenesis is an appealing therapeutic strategy, but to date, success has been elusive. We previously identified HEYL, a downstream target of Notch signaling, as an overexpressed gene in both breast cancer cells and as a tumor endothelial marker, suggesting that HEYL overexpression in both compartments may contribute to neoangiogenesis. Carcinomas arising in double transgenic Her2-neu/HeyL mice showed higher tumor vessel density and significantly faster growth than tumors in parental Her2/neu mice.

Sarcoma classification by DNA methylation profiling.

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate.

Characteristics and outcome of pediatric renal cell carcinoma patients registered in the International Society of Pediatric Oncology (SIOP) 93-01, 2001 and UK-IMPORT database: A report of the SIOP-Renal Tumor Study Group.

In children, renal cell carcinoma (RCC) is rare. This study is the first report of pediatric patients with RCC registered by the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG). Pediatric patients with histologically confirmed RCC, registered in SIOP 93-01, 2001 and UK-IMPORT databases, were included.

Identification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell Infiltration.

Extra-cranial malignant rhabdoid tumors (MRTs) and cranial atypical teratoid RTs (ATRTs) are heterogeneous pediatric cancers driven primarily by SMARCB1 loss. To understand the genome-wide molecular relationships between MRTs and ATRTs, we analyze multi-omics data from 140 MRTs and 161 ATRTs. We detect similarities between the MYC subgroup of ATRTs (ATRT-MYC) and extra-cranial MRTs, including global DNA hypomethylation and overexpression of HOX genes and genes involved in mesenchymal development, distinguishing them from other ATRT subgroups that express neural-like features.

High-risk blastemal Wilms tumor can be modeled by 3D spheroid cultures in vitro.

In vitro models represent a critical tool in cancer research to study tumor biology and to evaluate new treatment options. Unfortunately, there are no effective preclinical models available that represent Wilms tumor (WT) - the most common pediatric renal tumor. Especially the high-risk blastemal WT subtype is not represented by the few primary cell lines established until now.

The transcription factor Hey and nuclear lamins specify and maintain cell identity.

The inability of differentiated cells to maintain their identity is a hallmark of age-related diseases. We found that the transcription factor Hey supervises the identity of differentiated enterocytes (ECs) in the adult midgut. Lineage tracing established that Hey-deficient ECs are unable to maintain their unique nuclear organization and identity.