Pawel Buczkowicz
A5013452761- Glioma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- PARP inhibition in cancer therapy
- T-cell and Retrovirus Studies
- ATP Synthase and ATPases Research
- Acute Lymphoblastic Leukemia research
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Chromatin Remodeling and Cancer
- RNA modifications and cancer
- HIV/AIDS drug development and treatment
- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- Integrated Circuits and Semiconductor Failure Analysis
- Molecular Biology Techniques and Applications
- Genomic variations and chromosomal abnormalities
- Adrenal and Paraganglionic Tumors
- Single-cell and spatial transcriptomics
- Radiomics and Machine Learning in Medical Imaging
- Genomics and Rare Diseases
- Ocular Oncology and Treatments
- Cancer-related molecular mechanisms research
- Pancreatic and Hepatic Oncology Research
- Radiation Therapy and Dosimetry
- Ferroptosis and cancer prognosis
Hospital for Sick Children
2010-2022
Children's Mercy Hospital
2021
Pacific Biosciences (United States)
2021
University of Missouri–Kansas City
2021
SickKids Foundation
2010-2016
University of Toronto
2010-2016
Brain Tumour Research
2011-2014
Université de Lorraine
2012
Pediatric glioblastomas (GBM) including diffuse intrinsic pontine gliomas (DIPG) are devastating brain tumors with no effective therapy. Here, we investigated clinical and biological impacts of histone H3.3 mutations. Forty-two DIPGs were tested for Wild-type versus mutated (K27M-H3.3) subgroups compared HIST1H3B, IDH, ATRX TP53 mutations, copy number alterations outcome. K27M-H3.3 occurred in 71 %, mutations 77 % 9 DIPGs. more frequent older children (p < 0.0001). No G34V/R-H3.3, IDH1/2 or...
Diffuse intrinsic pontine glioma (DIPG) is one of the most devastating pediatric malignancies and for which no effective therapy exists. A major contributor to failure therapeutic trials assumption that biologic properties brainstem tumors in children are identical cerebral high-grade gliomas adults. better understanding biology DIPG itself needed order develop agents targeted more specifically these children's disease. Herein, we address this lack knowledge by performing first...
Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumour-related death in children. In majority cases diagnosis based on clinical and MRI findings, resulting scarcity pre-treatment specimens available to study. Our group has developed an autopsy-based protocol investigate histologic biologic spectrum DIPG. This also allowed us terminal pattern disease gain a better understanding what challenges we are facing treating Here, review 72 DIPG with well documented history...
To uncover the genetic events leading to transformation of pediatric low-grade glioma (PLGG) secondary high-grade (sHGG).We retrospectively identified patients with sHGG from a population-based cohort 886 PLGG long clinical follow-up. Exome sequencing and array CGH were performed on available samples followed by detailed analysis entire cohort. Clinical outcome data genetically distinct subgroups obtained.sHGG was observed in 2.9% PLGGs (26 patients). Patients had high frequency nonsilent...
Diffuse intrinsic pontine glioma (DIPG) and midline high-grade (mHGG) are lethal childhood brain tumors. Spatial genomic heterogeneity has been well-described in adult HGG but not comprehensively characterized pediatric HGG. We performed whole exome sequencing on 38-matched primary, contiguous, metastatic tumor sites from eight children with DIPG (n = 7) or mHGG 1) collected using a unique MRI-guided autopsy protocol. Validation was Sanger sequencing, Droplet Digital polymerase-chain...
Paediatric brain tumours arising in the thalamus present significant diagnostic and therapeutic challenges to physicians due their sensitive midline location. As such, genetic analysis for biomarkers aid diagnosis, prognosis treatment of these is needed. Here, we identified 64 thalamic gliomas with clinical follow-up characterized targeted genomic alterations using newly optimized droplet digital NanoString-based assays. The median age at diagnosis was 9.25 years (range, 0.63–17.55) survival...
PurposeThis study aimed to provide comprehensive diagnostic and candidate analyses in a pediatric rare disease cohort through the Genomic Answers for Kids program.MethodsExtensive of 960 families with suspected genetic disorders included short-read exome sequencing genome (srGS); PacBio HiFi long-read (HiFi-GS); variant calling single nucleotide variants (SNV), structural (SV), repeat variants; machine-learning prioritization. Structured phenotypes, prioritized variants, pedigrees were...
Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, lethal tumor in children. Unfortunately, many tumors resistant to this therapy. We sought identify ways sensitizing cells alkylating while leaving normal unharmed, increasing therapeutic response minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage genes, we identified novel sensitizers agents. In particular, base excision repair (BER) pathway,...
Pediatric high-grade astrocytomas (pHGA) and diffuse intrinsic pontine gliomas (DIPG) are devastating malignancies for which no effective therapies exist. We investigated the therapeutic potential of PARP1 inhibition in preclinical models pHGA DIPG. levels were characterized DIPG patient samples tumor-derived cell lines. The effects PARP inhibitors veliparib, olaparib, niraparib as monotherapy or radiosensitizers on viability, DNA damage, activity evaluated a panel Survival benefit was...
Pediatric high-grade astrocytomas (HGAs) account for 15-20% of all pediatric central nervous system tumors. These neoplasms predominantly involve the supratentorial hemispheres or pons--diffuse intrinsic pontine gliomas (DIPG). Assumptions that HGAs are biologically similar to adult have recently been challenged, and development effective therapeutic modalities DIPG HGA hinges on a better understanding their biological properties. Here, 20 (9 DIPGs 11 HGAs) were subject gene expression...
Pediatric ependymomas are highly recurrent tumors resistant to conventional chemotherapy. Telomerase, a ribonucleoprotein critical in permitting limitless replication, has been found be critically important for the maintenance of tumor-initiating cells (TICs). These TICs chemoresistant, repopulate tumor from which they identified, and drivers recurrence numerous cancers. In this study, telomerase enzymatic activity was directly measured inhibited assess therapeutic potential targeting...
The genomic alterations associated with cancers are numerous and varied, involving both isolated large-scale complex rearrangements (CGRs). Although the underlying mechanisms not well understood, CGRs have been implicated in tumorigenesis. Here, we introduce CouGaR, a novel method for characterizing structure of amplified CGRs, leveraging depth coverage (DOC) discordant pair-end mapping techniques. We applied our to whole-genome sequencing (WGS) samples from Cancer Genome Atlas identify at...
To determine whether the zinc finger transcription factors GLI1 to GLI3 and suppressor of fused (SUFU) components Sonic hedgehog signaling pathway may be prognostic markers potential therapeutic targets in pediatric medulloblastoma (MB), we investigated relationship expression these proteins prognosis MB 124 patients who had undergone surgery atthe Hospital for Sick Children (Toronto, Ontario, Canada). The expressions (p = 0.011) GLI2 0.003), but not 0.774) or SUFU 0.137), were associated...
Abstract Pediatric gliomas are the most commonly diagnosed brain cancer in children, accounting for approximately 50% of all cases. Work by our group and others has revealed recurrent histone mutations diffuse intrinsic pontine glioma (DIPG), astrocytomas that arise brainstem children boast a dismal median survival less than one year. In ~70% DIPG, mutation variant H3.3 or H3.1 at position 27 leads to substitution lysine methionine (K27M). When correlated clinical data, patients harbouring...
Abstract Diffuse intrinsic pontine glioma (DIPG) is a devastating paediatric brain tumor with no effective therapy and near 100% fatality. The failure of most therapies can be attributed to the delicate location these tumors choosing based on assumptions that DIPGs are molecularly similar adult disease. Recent studies have unravelled unique genetic make-up this cancer nearly 80% harbouring K27M-H3.3 or K27M-H3.1 mutation. However, still thought as one disease limited understanding drivers...
Pediatric gliomas are the most commonly diagnosed brain cancer in children, accounting for approximately 50% of all cases. Recently, we conducted genome-analysis diffuse intrinsic pontine glioma (DIPG), which specifically arises brainstem. Through this, identified a histone H3.3 mutation (a lysine-methionine substitution at position 27 [K27M]) 70% We then showed that H3.3K27M is negative prognostic marker DIPG patients independent histology. hypothesized similar role thalamic gliomas....
BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain tumor with no effective therapy and near 100% fatality. The failure of most therapies can be attributed to the delicate location these tumors choosing based on assumptions that DIPGs are molecularly similar adult disease. Recent studies have unraveled unique genetic make-up this cancer nearly 80% harboring K27M-H3.3 or K27M-H3.1 mutation. However, still thought as one disease limited understanding drivers...
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