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Open AccessPrecision-guided treatment in high-risk pediatric cancers
Recent research showed that precision medicine can identify new treatment strategies for patients with childhood cancers. However, it is unclear which patients will benefit most from precision-guided treatment...
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Article
Open AccessAtypical splicing variants in PKD1 explain most undiagnosed typical familial ADPKD
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of kidney failure and is primarily associated with PKD1 or PKD2. Approximately 10% of patients remain undiagnosed after stan...
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Open AccessIntrome accurately predicts the impact of coding and noncoding variants on gene splicing, with clinical applications
Predicting the impact of coding and noncoding variants on splicing is challenging, particularly in non-canonical splice sites, leading to missed diagnoses in patients. Existing splice prediction tools are comp...
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Open AccessA novel transcriptional signature identifies T-cell infiltration in high-risk paediatric cancer
Molecular profiling of the tumour immune microenvironment (TIME) has enabled the rational choice of immunotherapies in some adult cancers. In contrast, the TIME of paediatric cancers is relatively unexplored. ...
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Open AccessUnusual PDGFRB fusion reveals novel mechanism of kinase activation in Ph-like B-ALL
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Open AccessHistone H3-wild type diffuse midline gliomas with H3K27me3 loss are a distinct entity with exclusive EGFR or ACVR1 mutation and differential methylation of homeobox genes
Diffuse midline gliomas (DMG) harbouring H3K27M mutation are paediatric tumours with a dismal outcome. Recently, a new subtype of midline gliomas has been described with similar features to DMG, including loss...
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Open AccessDiagnostic classification of childhood cancer using multiscale transcriptomics
The causes of pediatric cancers’ distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multileve...
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Open AccessMeasurable residual disease analysis in paediatric acute lymphoblastic leukaemia patients with ABL-class fusions
ABL-class fusions including NUP214-ABL1 and EBF1-PDGFRB occur in high risk acute lymphoblastic leukaemia (ALL) with gene expression patterns similar to BCR-ABL-positive ALL. Our aim was to evaluate new DNA-based ...
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Open AccessGlutamine addiction promotes glucose oxidation in triple-negative breast cancer
Glutamine is a conditionally essential nutrient for many cancer cells, but it remains unclear how consuming glutamine in excess of growth requirements confers greater fitness to glutamine-addicted cancers. By ...
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Open AccessWhole-genome sequencing facilitates patient-specific quantitative PCR-based minimal residual disease monitoring in acute lymphoblastic leukaemia, neuroblastoma and Ewing sarcoma
Minimal residual disease (MRD) measurement is a cornerstone of contemporary acute lymphoblastic leukaemia (ALL) treatment. The presence of immunoglobulin (Ig) and T cell receptor (TCR) gene recombinations in l...
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Open AccessClinSV: clinical grade structural and copy number variant detection from whole genome sequencing data
Whole genome sequencing (WGS) has the potential to outperform clinical microarrays for the detection of structural variants (SV) including copy number variants (CNVs), but has been challenged by high false pos...
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Open AccessEfficacy of MEK inhibition in a recurrent malignant peripheral nerve sheath tumor
The prognosis of recurrent malignant peripheral nerve sheath tumors (MPNST) is dismal, with surgical resection being the only definitive salvage therapy. Treatment with chemoradiation approaches has not signif...
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Article
Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer
The Zero Childhood Cancer Program is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Using tumor and germline whole genome sequencing (WGS) and RNA sequ...
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Open AccessProteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer
Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understandi...
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Open AccessThe Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly
Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. ...
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Open AccessDevelopment and validation of a targeted gene sequencing panel for application to disparate cancers
Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targete...
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Denisovan, modern human and mouse TNFAIP3 alleles tune A20 phosphorylation and immunity
Resisting and tolerating microbes are alternative strategies to survive infection, but little is known about the evolutionary mechanisms controlling this balance. Here genomic analyses of anatomically modern h...
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Increased Diagnostic Yield of Spastic Paraplegia with or Without Cerebellar Ataxia Through Whole-Genome Sequencing
Inherited disorders of spasticity or ataxia exist on a spectrum with overlap** causative genes and phenotypes. We investigated the use of whole-genome sequencing (WGS) to detect a genetic cause when consider...
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Open AccessDeep multi-region whole-genome sequencing reveals heterogeneity and gene-by-environment interactions in treatment-naive, metastatic lung cancer
Our understanding of genomic heterogeneity in lung cancer is largely based on the analysis of early-stage surgical specimens. Here we used endoscopic sampling of paired primary and intrathoracic metastatic tum...
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High Degree of Genetic Heterogeneity for Hereditary Cerebellar Ataxias in Australia
Genetic testing strategies such as next-generation sequencing (NGS) panels and whole genome sequencing (WGS) can be applied to the hereditary cerebellar ataxias (HCAs), but their exact role in the diagnostic p...
