A5101814981- Childhood Cancer Survivors' Quality of Life
- Acute Lymphoblastic Leukemia research
- Cancer Genomics and Diagnostics
- Genomics and Rare Diseases
- BRCA gene mutations in cancer
- Neuroblastoma Research and Treatments
- Glioma Diagnosis and Treatment
- RNA modifications and cancer
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Pancreatic and Hepatic Oncology Research
- Genomics and Phylogenetic Studies
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Acute Myeloid Leukemia Research
- Mesenchymal stem cell research
- RNA Research and Splicing
- Health, Environment, Cognitive Aging
- Organ Transplantation Techniques and Outcomes
- Cancer, Hypoxia, and Metabolism
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
- Cancer-related cognitive impairment studies
- Sarcoma Diagnosis and Treatment
- Cancer-related gene regulation
St. Jude Children's Research Hospital
2016-2025
Dana-Farber Cancer Institute
2025
Harvard University
2025
Weatherford College
2024
Disco (Germany)
2024
Beijing Normal University
2024
Nanjing Medical University
2024
Chinese Institute for Brain Research
2024
University of Pennsylvania Health System
2013-2024
Shaanxi Normal University
2024
Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into biology. Here we present comprehensive analysis of genetic alterations in pan-cancer cohort including 961 tumours from children, adolescents, young adults, comprising 24 distinct molecular cancer. Using standardized workflow, identified marked terms mutation frequency significantly mutated genes comparison previously analysed adult cancers....
The prevalence and spectrum of predisposing mutations among children adolescents with cancer are largely unknown. Knowledge such may improve the understanding tumorigenesis, direct patient care, enable genetic counseling patients families.In 1120 younger than 20 years age, we sequenced whole genomes (in 595 patients), exomes 456), or both 69). We analyzed DNA sequences 565 genes, including 60 that have been associated autosomal dominant cancer-predisposition syndromes, for presence germline...
Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight need molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify full spectrum of driver genes molecular processes that operate in medulloblastoma subgroups. Here we analyse somatic landscape across 491 sequenced samples heterogeneity among 1,256 epigenetically analysed cases, subgroup-specific...
Abstract Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated cells from diverse lineages. Pan-cancer analyses have been performed for adult 1,2,3,4 but not paediatric cancers, which commonly occur developing mesodermic rather than epithelial tissues 5 . Here we present a study somatic alterations, including single nucleotide variants, small insertions or...
Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma genes have not been defined and screening guidelines for genetic counselling testing paediatric patients are available. We aimed to assess define these provide evidence future guidelines.
Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing copy number alteration analysis. Recurrent gene mutations fusions tested in an additional 87 93 patients. Among the 29 newly identified in-frame fusions, those involving MEF2D ZNF384 clinically relevant demonstrated to perturb differentiation, EP300-ZNF384 inducing mice. Eight expression subgroups associated characteristic genetic...
Abstract Effective data sharing is key to accelerating research improve diagnostic precision, treatment efficacy, and long-term survival in pediatric cancer other childhood catastrophic diseases. We present St. Jude Cloud (https://www.stjude.cloud), a cloud-based data-sharing ecosystem for accessing, analyzing, visualizing genomic from >10,000 patients with survivors, >800 sickle cell patients. Harmonized totaling 1.25 petabytes are freely available, including 12,104 whole...
Abstract Extensive research has focused on transplantation of pluripotent stem cells for the treatment central nervous system disorders, therapeutic potential cell therapy injured peripheral nerves is largely unknown. We used a rat sciatic nerve transection model to test ability implanted embryonic (ES) cell-derived neural progenitor (ES-NPCs) in promoting repair severely nerve. Mouse ES were neurally induced vitro; enhanced expression and/or secretion growth factors detected differentiating...
Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. To better understand neuroblastoma pathogenesis, here we analyze whole-genome, whole-exome and/or transcriptome data from 702 samples. Forty percent of samples harbor at least one recurrent driver gene alteration and most aberrations, including MYCN, ATRX, TERT alterations, differ in frequency by age. MYCN alterations occur median 2.3 years age, 3.8 years, ATRX 5.6 years. COSMIC mutational signature 18, previously...
Purpose Childhood cancer survivors are at increased risk of subsequent neoplasms (SNs), but the germline genetic contribution is largely unknown. We assessed pathogenic/likely pathogenic (P/LP) mutations in predisposition genes to their SN risk. Patients and Methods Whole-genome sequencing (30-fold) was performed on samples from childhood who were ≥ 5 years since initial diagnosis participants St Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical...
Transplantation using stem cells including bone marrow mesenchymal (BMSCs) is emerging as a potential regenerative therapy after ischemic attacks in the heart and brain. The migration capability of transplanted critical cellular function for tissue repair. Based on our recent observations that hypoxic preconditioning (HP) has multiple benefits improving cell potassium Kv2.1 channel acts promoter focal adhesion kinase (FAK) activation motility, present investigation tested hypothesis HP...
Relapse of acute lymphoblastic leukemia (ALL) remains a leading cause childhood death. Prior studies have shown clonal mutations at relapse often arise from relapse-fated subclones that exist diagnosis. However, the genomic landscape, evolutionary trajectories and mutational mechanisms driving are incompletely understood. In an analysis 92 cases relapsed ALL, incorporating multimodal DNA RNA sequencing, deep digital tracking xenografting to formally define structure, we identify 50...
Abstract To discover driver fusions beyond canonical exon-to-exon chimeric transcripts, we develop CICERO, a local assembly-based algorithm that integrates RNA-seq read support with extensive annotation for candidate ranking. CICERO outperforms commonly used methods, achieving 95% detection rate 184 independently validated including internal tandem duplications and other non-canonical events in 170 pediatric cancer transcriptomes. Re-analysis of TCGA glioblastoma unveils previously...
Abstract Aggressive cancers often have activating mutations in growth-controlling oncogenes and inactivating tumor-suppressor genes. In neuroblastoma, amplification of the MYCN oncogene inactivation ATRX gene correlate with high-risk disease poor prognosis. Here we show that are mutually exclusive across all ages stages neuroblastoma. Using human cell lines mouse models, found elevated expression incompatible. Elevated levels promote metabolic reprogramming, mitochondrial dysfunction,...
Genomic studies of pediatric cancer have primarily focused on specific tumor types or high-risk disease. Here, we used a three-platform sequencing approach, including whole-genome (WGS), whole-exome (WES), and RNA (RNA-seq), to examine germline genomes from 309 prospectively identified children with newly diagnosed (85%) relapsed/refractory (15%) cancers, unselected for type. Eighty-six percent patients harbored diagnostic (53%), prognostic (57%), therapeutically relevant (25%), and/or...