John Easton
A5025610733- Cancer Genomics and Diagnostics
- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Neuroblastoma Research and Treatments
- Epigenetics and DNA Methylation
- Childhood Cancer Survivors' Quality of Life
- RNA modifications and cancer
- Genomics and Rare Diseases
- Chronic Myeloid Leukemia Treatments
- Single-cell and spatial transcriptomics
- Sarcoma Diagnosis and Treatment
- Glioma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Genomics and Phylogenetic Studies
- Molecular Biology Techniques and Applications
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Genetic factors in colorectal cancer
- Protein Kinase Regulation and GTPase Signaling
- Genomics and Chromatin Dynamics
- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Cancer-related molecular mechanisms research
- Lung Cancer Treatments and Mutations
- DNA Repair Mechanisms
St. Jude Children's Research Hospital
2016-2025
University of Strathclyde
2024
Roslin Institute
2021
University of Edinburgh
2021
Institute of Genetics and Cancer
2021
Western General Hospital
2021
Weatherford College
2021
Flint Institute Of Arts
2021
Edinburgh Royal Infirmary
2021
Northwestern University
2020
Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing 12 ETP ALL cases and assessed the frequency identified somatic mutations in 94 cases. was characterized by activating genes regulating cytokine receptor RAS signalling (67% cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 EP300)...
Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR–ABL1–positive ALL, alterations lymphoid transcription factor genes, and poor outcome. The frequency spectrum genetic in Ph-like ALL its responsiveness tyrosine kinase inhibition are undefined, especially adolescents adults.
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...
Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. Here, to identify mutations that drive medulloblastoma, we sequenced the entire genomes of 37 tumours and matched normal blood. One-hundred thirty-six genes harbouring somatic in this discovery set were an additional 56 medulloblastomas. Recurrent detected 41 not yet implicated medulloblastoma; several target distinct components epigenetic machinery different disease subgroups, such as regulators H3K27...
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...
Pediatric osteosarcoma is characterized by multiple somatic chromosomal lesions, including structural variations (SVs) and copy number alterations (CNAs). To define the landscape of mutations in pediatric osteosarcoma, we performed whole-genome sequencing DNA from 20 tumor samples matched normal tissue a discovery cohort, as well 14 validation cohort. Single-nucleotide (SNVs) exhibited pattern localized hypermutation called kataegis 50% tumors. We identified p53 pathway lesions all tumors...
Retinoblastoma is an aggressive childhood cancer of the developing retina that initiated by biallelic loss RB1. Tumours progress very quickly following RB1 inactivation but underlying mechanism not known. Here we show retinoblastoma genome stable, multiple pathways can be epigenetically deregulated. To identify mutations cooperate with loss, performed whole-genome sequencing retinoblastomas. The overall mutational rate was low; only known gene mutated. We then evaluated role in stability and...
Ewing sarcoma is a primary bone tumor initiated by EWSR1-ETS gene fusions. To identify secondary genetic lesions that contribute to progression, we performed whole-genome sequencing of 112 samples and matched germline DNA. Overall, tumors had relatively few single-nucleotide variants, indels, structural copy-number alterations. Apart from whole chromosome arm changes, the most common somatic mutations were detected in STAG2 (17%), CDKN2A (12%), TP53 (7%), EZH2, BCOR, ZMYM3 (2.7% each)....
Abstract There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the architecture 20 pediatric B-acute lymphoblastic leukaemias from diagnosis relapse. We show that diversity comparable at relapse survival not associated with mutation burden. Six pathways were frequently mutated, NT5C2 , CREBBP WHSC1 TP53 USH2A NRAS IKZF1 mutations enriched Half had multiple subclonal in a pathway or gene...