A5018963612- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- Childhood Cancer Survivors' Quality of Life
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Cancer-related molecular mechanisms research
- PARP inhibition in cancer therapy
- RNA Interference and Gene Delivery
- Neuroblastoma Research and Treatments
- Cancer therapeutics and mechanisms
Hospital for Sick Children
2022-2024
Mount Sinai Hospital
2023
University of Toronto
2023
We conducted integrative somatic-germline analyses by deeply sequencing 864 cancer-associated genes, complete genomes and transcriptomes for 300 mostly previously treated children adolescents/young adults with cancer of poor prognosis or rare tumors enrolled in the SickKids Cancer Sequencing (KiCS) program. Clinically actionable variants were identified 56% patients. Improved diagnostic accuracy led to modified management a subset. Therapeutically targetable (54% patients) unanticipated...
Abstract Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition associated with germline TP53 pathogenic variants. Here, we perform whole-genome sequence (WGS) analysis of tumors from 22 patients We observe somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous recombination genes as well mutational signatures prior chemotherapy. identify near-ubiquitous early loss heterozygosity , gain the mutant allele. This occurs earlier in these compared to...
Abstract Survivors of pediatric cancer face lifelong battles with severe morbidities, which includes a significant risk recurrence. Pre-existing genetic variation within primary tumors may offer certain cell populations an evolutionary advantage, increasing the likelihood that some will be resistant to treatment. But inherent complexity tumor means finding these markers resistance has yet fully explored across childhood cancer. To address this, we developed pipeline combines clonal evolution...
Abstract Survivors of pediatric cancer face lifelong battles with severe morbidities, including a significant risk recurrence. Pre-existing genetic variation within primary tumors give certain cell populations an evolutionary advantage, increasing the likelihood treatment resistance and relapse. The rarity limited clinical metadata have restricted comprehensive studies on chemoresistance development. I aim to characterize timing in common childhood cancers. developed pipeline combining...
Abstract Treatment at a young age places survivors of childhood cancers significantly elevated risk developing life-threatening conditions such as cardiac dysfunction and secondary neoplasms. To better define the genomic impact cancer therapy in children, we studied diverse cohort tumors that had been heavily treated with multiple chemotherapies. We retrospectively collected detailed therapeutic data (including drug dosage for each treatment cycle) three cohorts aggressive hard-to-cure...