Lawrence Bower
A5067303287- Cancer Genomics and Diagnostics
- Esophageal Cancer Research and Treatment
- Genomic variations and chromosomal abnormalities
- Molecular Biology Techniques and Applications
- Gastrointestinal Tumor Research and Treatment
- Cancer-related gene regulation
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Gastric Cancer Management and Outcomes
- Esophageal and GI Pathology
- Genomics and Rare Diseases
- Cancer Cells and Metastasis
- Genomics and Phylogenetic Studies
- Parathyroid Disorders and Treatments
- Genetic factors in colorectal cancer
- Innovative Microfluidic and Catalytic Techniques Innovation
- DNA and Biological Computing
- Microbial Community Ecology and Physiology
- Single-cell and spatial transcriptomics
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Lung Cancer Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Cancer Immunotherapy and Biomarkers
Cancer Research UK Cambridge Center
2017-2022
Cancer Research UK
2014-2022
University of Cambridge
2014-2022
MRC Cancer Unit
2018
Medical Research Council
2018
European Bioinformatics Institute
2009-2012
Wellcome Sanger Institute
2009
Abstract As whole-genome sequencing for cancer genome analysis becomes a clinical tool, full understanding of the variables affecting output is required. Here using tumour-normal sample pairs from two different types cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct benchmarking exercise within context International Cancer Genome Consortium. We compare methods, pipelines validation methods. show that PCR-free methods increasing depth to ∼100 × shows benefits, as long...
Abstract Esophageal adenocarcinoma (EAC) incidence is increasing while 5-year survival rates remain less than 15%. A lack of experimental models has hampered progress. We have generated clinically annotated EAC organoid cultures that recapitulate the morphology, genomic, and transcriptomic landscape primary tumor including point mutations, copy number alterations, mutational signatures. Karyotyping confirmed polyclonality reflecting clonal architecture tumor. Furthermore, subclones underwent...
Abstract Background This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response neoadjuvant chemotherapy in oesophageal adenocarcinoma. Methods A questionnaire was distributed 11 UK upper gastrointestinal cancer centres determine the use assessment chemotherapy. Records consecutive patients undergoing oesophagogastric resection at seven between January 2000 and December 2013 were reviewed. Pathological assessed using Mandard Tumour...
The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena/) collects, maintains and presents comprehensive nucleic acid sequence related information as part of the permanent public scientific record. Here, we provide brief updates on ENA content developments major service enhancements in 2012 describe more detail two important areas development policy that are driven by ongoing growth sequencing technologies. First, data warehouse, a resource for which programmatic entry point to...
The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) is Europe's primary nucleotide sequence archival resource, safeguarding open data access, engaging in worldwide collaborative exchange and integrating with the scientific publication process. ENA has made significant contributions to arena as an active proponent of extending traditional collaboration cover capillary next-generation sequencing information. We have continued co-develop metadata representation formats our...
The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes individual patients considering all types damaging simultaneously. Analysing 261 EACs from the OCCAMS Consortium, discover helper that, alongside well-known drivers, promote cancer. We confirm robustness our approach 107 additional EACs. Unlike...
The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is heterogeneous, chemoresistant tumor for which availability and size pretreatment endoscopic are limiting. This study compares whole-genome sequencing data obtained chemo-naive chemo-treated samples. quality whole-genomic comparable across all regardless status. Inclusion collected post-chemotherapy...
<ns4:p>Esophageal adenocarcinoma (EAC) is highly mutated and molecularly heterogeneous. The number of cell lines available for study limited their genome has been only partially characterized. availability an accurate annotation mutational landscape crucial experimental design correct interpretation genotype-phenotype findings. We performed high coverage, paired end whole sequencing on eight EAC lines—ESO26, ESO51, FLO-1, JH-EsoAd1, OACM5.1 C, OACP4 OE33, SK-GT-4—all verified against...
Abstract New biological tools are required to understand the functional significance of genetic events revealed by whole genome sequencing (WGS) studies in oesophageal adenocarcinoma (OAC). The MFD-1 cell line was isolated from a 55-year-old male with OAC without recombinant-DNA transformation. Somatic variations MFD-1, tumour, normal oesophagus, and leucocytes were analysed SNP6. WGS performed tumour leucocytes. RNAseq two classic lines FLO1 OE33. Transposase-accessible chromatin (ATAC-seq)...
Cancers occurring at the gastroesophageal junction (GEJ) are classified as predominantly esophageal or gastric, which is often difficult to decipher. We hypothesized that transcriptomic profile might reveal molecular subgroups could help define tumor origin and behavior beyond anatomical location. The gene expression profiles of 107 treatment‐naïve, intestinal type, adenocarcinomas were assessed by Illumina‐HTv4.0 beadchip. Differential (limma), unsupervised subgroup assignment (mclust)...
Esophageal adenocarcinoma (EAC) develops in an inflammatory microenvironment with reduced microbial diversity, but mechanisms for these influences remain poorly characterized. We hypothesized that mutations targeting the Toll-like receptor (TLR) pathway could disrupt innate immune signaling and promote a favors tumorigenesis. Through interrogating whole genome sequencing data from 171 EAC patients, we showed non-synonymous collectively affect TLR 25/171 (14.6%, PathScan p = 8.7x10-5) tumors....
Abstract Esophageal Adenocarcinoma (EAC) is a poor prognosis cancer type with rapidly rising incidence. Our understanding of genetic events which drive EAC development limited and there are few molecular biomarkers for prognostication or therapeutics. We have accumulated cohort 551 genomically characterised EACs (73% WGS 27% WES) clinical annotation matched RNA-seq. Using variety driver gene detection methods, we discover 77 genes novel) 21 non-coding elements (95% novel), describe mutation...
Abstract The emergence of next generation DNA sequencing technology is enabling high-resolution cancer genome analysis. Large-scale projects like the International Cancer Genome Consortium (ICGC) are systematically scanning genomes to identify recurrent somatic mutations. Second sequencing, however, still an evolving and procedures, both experimental analytical, constantly changing. Thus research community defining a set best practices for data analysis, with no single protocol emerging...
Abstract Large-scale cancer genome studies suggest that tumors are driven by somatic copy number alterations (SCNAs) or single-nucleotide variants (SNVs). Due to the low-cost, clinical use of genomics assays is biased towards targeted gene panels, which identify SNVs. There a need for comparably low-cost and simple assay high-resolution SCNA profiling. Here we present our method, conliga, infers profiles from assay.
Abstract Continual evolution of cancer makes it challenging to predict clinical outcomes. Highly varied and unpredictable patient outcomes in esophageal adenocarcinoma (EAC) prompted us question the pattern timing metastatic spread. Whole genome sequencing phylogenetic analysis 396 samples across 18 EAC cases demonstrated a stellate on trees 90% cases. The age-dependent trinucleotide signature, which can serve as molecular clock, was absent or reduced branches beyond trunk most...
Somatic copy number alterations (SCNAs) are an important class of genomic alteration in cancer. They frequently observed cancer samples, with studies showing that, on average, SCNAs affect 34% a cell's genome. Furthermore, have been shown to be major drivers tumour development and associated response therapy prognosis. Large-scale genome suggest that tumours driven by somatic or single-nucleotide variants (SNVs). Despite the frequency their clinical relevance, use genomics assays clinic is...