A5063797922- Glioma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Neuroblastoma Research and Treatments
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Genetic factors in colorectal cancer
- Single-cell and spatial transcriptomics
- Molecular Biology Techniques and Applications
- Cancer-related molecular mechanisms research
- Blood disorders and treatments
- Carbohydrate Chemistry and Synthesis
- Protein Tyrosine Phosphatases
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Ferroptosis and cancer prognosis
- Multiple and Secondary Primary Cancers
- Bacterial Identification and Susceptibility Testing
- Advanced Electron Microscopy Techniques and Applications
- Neutropenia and Cancer Infections
- Childhood Cancer Survivors' Quality of Life
- Genomics and Chromatin Dynamics
- PI3K/AKT/mTOR signaling in cancer
- Cancer Diagnosis and Treatment
- Neurofibromatosis and Schwannoma Cases
Discovery Institute
2024-2025
Sanford Burnham Prebys Medical Discovery Institute
2024-2025
University of California, San Diego
2021-2024
Rady Children's Hospital-San Diego
2021-2024
UCSF Benioff Children's Hospital
2020
Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution drug resistance and poor outcomes. Applying computational methods for the detection reconstruction ecDNA across a retrospective cohort 481 medulloblastoma from 465 patients, we identify circular 82 patients (18%). Patients with ecDNA-positive were more than twice as likely to relapse three times die within 5 years diagnosis. A subset harbored multiple lineages, each...
Ependymoma is a tumor of the brain or spinal cord. The two most common and aggressive molecular groups ependymoma are supratentorial ZFTA-fusion associated posterior fossa group A. In both groups, tumors occur mainly in young children frequently recur after treatment. Although mechanisms underlying these diseases have recently been uncovered, they remain difficult to target innovative therapeutic approaches urgently needed. Here, we use genome-wide chromosome conformation capture (Hi-C),...
SUMMARY Extrachromosomal circular DNA (ecDNA) is an important driver of aggressive tumor growth, promoting high oncogene copy number, intratumoral heterogeneity, accelerated evolution drug resistance, enhancer rewiring, and poor outcome. ecDNA has been reported in medulloblastoma (MB), the most common malignant pediatric brain tumor, but landscape its association with specific MB subgroups, impact on potential clinical implications, are not known. We assembled a retrospective cohort 468...
Abstract Circular extrachromosomal DNA (ecDNA, also known as double minutes, dm) has emerged a driver of oncogenic copy number amplification, intratumoral heterogeneity, tumor evolution and therapy resistance. We recently screened the whole genomes 481 medulloblatomas for ecDNA concluded that medulloblastoma tumors harboring are more than twice likely to progress within 5 years diagnosis. To evaluate frequency clincical impact across spectrum childhood cancers, we performed retrospective...
Abstract BACKGROUND Comprehensive molecular characterization of pediatric brain tumors has led to a more refined diagnosis. However, the feasibility performing multi-omic and functional precision medicine approaches using ex-vivo drug screening in clinical setting is unknown. METHODS Patients with newly diagnosed or recurrent central nervous system were enrolled study analysis including whole genome trio germline sequencing, tumor exome/RNA RNA-based DiSCoVER analysis, methylation profiling,...
Abstract BACKGROUND Circular extrachromosomal DNA (ecDNA) is a common form of oncogene amplification in aggressive cancers and promising target for improved cancer therapy. The frequency diversity ecDNA has been described different types adult selected childhood such as neuroblastoma medulloblastoma. However, the its association with survival not comprehensively analyzed across spectrum pediatric cancers. METHODS We performed pan-cancer study which we mined large genomics repositories...
Abstract BACKGROUND Children with brain and spinal cord tumors are at higher risk for sleep disruption. The incidence characteristics of difficulties in this population is not well understood. Our aim to use survey chart review retrospectively prospectively evaluate the frequency, severity, types experienced by pediatric patients who have spine tumors. METHODS Pediatric a diagnosis or tumor their parents were surveyed three time points during routine visits neuro-oncology team. Parents...
ABSTRACT Circular extrachromosomal DNA (ecDNA) can drive tumor initiation, progression and resistance in some of the most aggressive cancers is emerging as a promising anti-cancer target. However, detection currently requires costly whole-genome sequencing (WGS) or labor-intensive cytogenetic FISH imaging, limiting its application routine clinical diagnosis. To overcome this, we developed ecPath ( ec from histo path ology ) , computational method for predicting ecDNA status routinely...
Bevacizumab-based therapies have been utilized as single or combination therapy of refractory/recurrent pediatric low-grade gliomas. Its efficacy for symptomatic cervicomedullary gliomas (cmLGGs) in the upfront and recurrent setting is less known. We report our retrospective institutional experience from 2015 to 2021 with single-agent bevacizumab cmLGG. Six consecutive patients (4 female, ages 2 12 y) newly diagnosed (n=3) recurrent/refractory nondisseminated cmLGG (5/6 biopsy-proven,...
Abstract Extrachromosomal circular DNA (ecDNA) is an important driver of aggressive cancers, including medulloblastoma (MB), the most common malignant pediatric brain tumor. To assess clinical importance ecDNA in MB, we applied computational methods to detect genomes a cohort 468 MB patients and 31 model systems. Among patients, was detected 18% tumors carried threefold greater risk mortality. Affected genomic loci harbor up hundredfold amplification oncogenes MYC, MYCN, TERT, other novel...
Abstract Circular extrachromosomal DNA (ecDNA) is an important driver of aggressive cancers. Its frequency and impact on the spectrum pediatric cancers has yet to be fully described. To determine ecDNA prevalence in various cancer types, we accessed whole genome sequencing (WGS) data Children’s Brain Tumor Network (CBTN) St. Jude cloud genomics platforms utilized bioinformatics tools Amplicon Architect (AA) Classifier (AC) reconstruct sequence structures. We then identified which genes were...
Abstract Background Levofloxacin prophylaxis in pediatric oncology patients with chemotherapy-induced severe prolonged neutropenia has been shown to reduce risk for febrile and systemic infections. With increased use of there is concern development antibiotic-resistant We analyzed bloodstream infections (BSI) exposed levofloxacin during neutropenic episodes determine the rate antibiotic resistance Methods performed a retrospective chart review who received between January 2015 – December...
Abstract Extrachromosomal circular DNA (ecDNA) is an important driver of aggressive cancers, including medulloblastoma (MB), the most common malignant pediatric brain tumor. Our study’s aim to better understand how ecDNA containing cells can potentiate growth. EcDNA’s role in development treatment resistance and association with poor outcomes hypothesized arise from its contribution intra-tumoral heterogeneity potential promote oncogene dependency switching. To analyze distribution ecDNA, we...
Abstract Extrachromosomal circular DNA (ecDNA) is an important driver of aggressive cancers, including medulloblastoma (MB), the most common malignant pediatric brain tumor. To assess clinical import ecDNA in MB, we applied computational methods to detect genomes a cohort 468 MB patients and 31 model systems. Among patients, was detected 18% tumors carried threefold greater risk mortality. Between sequential patient biopsies at initial diagnosis subsequent relapse, observed frequent...
Abstract Extrachromosomal circular DNA (ecDNA) is an important driver of aggressive cancers. Its frequency and impact on pediatric cancers has yet to be fully described. To determine the ecDNA prevalence in various cancer types, we accessed whole genome sequencing (WGS) data Children’s Brain Tumor Network (CBTN) St. Jude cloud genomics platforms utilized bioinformatics tools Amplicon Architect (AA) Classifier (AC) reconstruct sequence structures. We then identified which genes were amplified...
Abstract Extrachromosomal circular DNA (ecDNA) is an important driver of aggressive cancers, including medulloblastoma (MB), the most common pediatric brain tumor. To assess clinical importance ecDNA in MB, we applied computational methods to detect genomes a cohort 468 MB patients and 31 model systems. Among patients, was detected 18% tumors carried over twofold greater risk mortality. Affected genomic loci harbor up hundredfold amplification oncogenes MYC, MYCN, TERT, other novel putative...