Clare Puttick
A5044494878- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Immune responses and vaccinations
- Lung Cancer Treatments and Mutations
- Genomics and Rare Diseases
- DNA Repair Mechanisms
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Cancer-related molecular mechanisms research
- Genetic factors in colorectal cancer
- RNA and protein synthesis mechanisms
- Molecular Biology Techniques and Applications
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Genomics and Phylogenetic Studies
- Lung Cancer Diagnosis and Treatment
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Ferroptosis and cancer prognosis
- Radiomics and Machine Learning in Medical Imaging
- Prostate Cancer Treatment and Research
The Francis Crick Institute
2019-2025
Cancer Research UK
2023-2025
London Cancer
2023-2025
CRUK Lung Cancer Centre of Excellence
2023-2025
University College London
2022-2025
UNSW Sydney
2014-2022
Garvan Institute of Medical Research
2016-2022
Macquarie University
2022
Royal North Shore Hospital
2022
Northern Sydney Local Health District
2022
Lung cancer is the leading cause of cancer-associated mortality worldwide
Abstract B cells are frequently found in the margins of solid tumours as organized follicles ectopic lymphoid organs called tertiary structures (TLS) 1,2 . Although TLS have been to correlate with improved patient survival and response immune checkpoint blockade (ICB), underlying mechanisms this association remain elusive Here we investigate lung-resident cell responses patients from TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) other lung cancer cohorts, a...
Abstract Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance therapy 1 . Here, using paired whole-exome RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell tumours from 347 out of the first 421 patients prospectively recruited into TRACERx study 2,3 Analyses 947 tumour regions, representing both primary metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate transcriptome...
Abstract Whole genome sequencing (WGS) improves Mendelian disorder diagnosis over whole exome (WES); however, additional diagnostic yields and costs remain undefined. We investigated differences between cost outcomes of WGS WES in a cohort with suspected disorders. was performed 38 WES-negative families derived from 64 family that previously underwent WES. For new diagnoses, contemporary reanalysis determined whether variants were diagnosable by original or unique to WGS. Diagnostic rates...
Abstract Understanding the role of tumor microenvironment (TME) in lung cancer is critical to improving patient outcomes. We identified four histology-independent archetype TMEs treatment-naïve early-stage using imaging mass cytometry TRACERx study (n = 81 patients/198 samples/2.3 million cells). In immune-hot adenocarcinomas, spatial niches T cells and macrophages increased with clonal neoantigen burden, whereas such an increase was observed for plasma B immune-excluded squamous cell...
Abstract APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when expression is induced during cancer development remains to be defined. Here we show that specific genes upregulated breast ductal carcinoma situ, and preinvasive lung lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx invasive non–small cell (NSCLC) lesions. find APOBEC3B exacerbates DNA replication stress chromosomal...
<h3>Objective</h3> To assess the benefits and limitations of whole genome sequencing (WGS) compared to exome (ES) or multigene panel (MGP) in molecular diagnosis developmental epileptic encephalopathies (DEE). <h3>Methods</h3> We performed WGS 30 comprehensively phenotyped DEE patient trios that were undiagnosed after first-tier testing, including chromosomal microarray either research ES (n = 15) diagnostic MGP 15). <h3>Results</h3> Eight diagnoses made 15 individuals who received prior...
PurposeThe utility of genome sequencing (GS) in the diagnosis suspected pediatric mitochondrial disease (MD) was investigated.MethodsAn Australian cohort 40 patients with clinical features suggestive MD were classified using modified Nijmegen severity scoring into definite (17), probable and possible (6) groups. Trio GS performed DNA extracted from patient parent blood. Data analyzed for single-nucleotide variants, indels, structural variants.ResultsA definitive gene molecular made 15 cases...
<h3>Background and Objectives</h3> Mitochondrial diseases (MDs) are the commonest group of heritable metabolic disorders. Phenotypic diversity can make molecular diagnosis challenging, causative genetic variants may reside in either mitochondrial or nuclear DNA. A single comprehensive diagnostic test would be highly useful transform field. We applied whole-genome sequencing (WGS) to evaluate variant detection rate capacity this technology with a view simplifying improving MD pathway....
Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss heterozygosity (LOH), allele-specific mutation measurement expression repression (MHC Hammer). identified extensive variability in HLA allelic pervasive alternative splicing normal lung breast tissue. In TRACERx TCGA cohorts, 61% adenocarcinoma (LUAD), 76% squamous cell carcinoma (LUSC) 35% estrogen...
Abstract Neoantigen vaccines are under investigation for various cancers, including epidermal growth factor receptor ( EGFR )-driven lung cancers 1,2 . We tracked the phylogenetic history of an mutant cancer treated with erlotinib, osimertinib, radiotherapy and a personalized neopeptide vaccine (NPV) targeting ten somatic mutations, exon 19 deletion (ex19del). The ex19del mutation was clonal, but is likely to have appeared after whole-genome doubling (WGD) event. Following osimertinib NPV...
Abstract Population health research is increasingly focused on the genetic determinants of healthy ageing, but there no public resource whole genome sequences and phenotype data from elderly individuals. Here we describe first release Medical Genome Reference Bank (MGRB), comprising sequence 2570 Australians depleted for cancer, cardiovascular disease, dementia. We analyse MGRB single-nucleotide, indel structural variation in nuclear mitochondrial genomes. individuals have fewer...
Mitochondrial diseases (MDs) are the most common group of inherited metabolic disorders and often challenging to diagnose due extensive genotype-phenotype heterogeneity. MDs caused by mutations in nuclear or mitochondrial genome, where pathogenic variants usually heteroplasmic typically at much lower allelic fraction blood than affected tissues. Both genomes can now be readily analyzed using whole genome sequencing (WGS), but variant detection methods fail detect low heteroplasmy genome. We...
Abstract Introduction Minimal residual disease (MRD) detection in solid tumors describes isolation of circulating tumor DNA (ctDNA) molecules plasma following definitive treatment a cancer. Detection MRD surgical excision categorizes patients as high risk for recurrence. Establishing an approach to treating early-stage NSCLC will facilitate escalation standard care (SoC) only destined relapse from their cancer and overcome challenges associated with conventional adjuvant drug-trial design....
Abstract Human tumors are diverse in their natural history and response to treatment, which part results from genetic transcriptomic heterogeneity. In clinical practice, single-site needle biopsies used sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution the sampling bias problem analyzing multiregion whole-exome RNA sequencing data for 450 tumor regions 184 patients...
Abstract Recognition and elimination of pathogens cancer cells depend on the adaptive immune system. Thus, accurate quantification subsets is vital for precision medicine. We present lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell B fractions, class switching clonotype diversity whole-genome data at depths as low 5× coverage. By applying ImmuneLENS to 100,000 Genomes Project, we identify genes enriched with somatic mutations in cell-rich tumors,...
Abstract Checkpoint inhibitors (CPIs) augment adaptive immunity. Systematic pan-tumor analyses may reveal the relative importance of tumour cell intrinsic and microenvironmental features underpinning CPI sensitization. Here we collated whole-exome transcriptomic data for >1000 CPI-treated patients across eight tumor-types, utilizing standardized bioinformatics-workflows clinical outcome-criteria to validate multivariate predictors CPI-sensitization. Clonal-TMB was strongest predictor...
Abstract Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development precision oncology treatments based on a tumour’s molecular profile. We aimed to develop targeted gene panel for application disparate cancer types with particular focus tumours head and neck, plus test utility in liquid biopsy. The final designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected...