A5055025757- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Liver physiology and pathology
- Colorectal Cancer Treatments and Studies
- BRCA gene mutations in cancer
- Inflammatory Bowel Disease
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Screening and Detection
- Telomeres, Telomerase, and Senescence
- Breast Cancer Treatment Studies
- Lung Cancer Treatments and Mutations
- Cancer, Lipids, and Metabolism
- Bioinformatics and Genomic Networks
- Ovarian cancer diagnosis and treatment
- TGF-β signaling in diseases
- Genomics and Chromatin Dynamics
- Angiogenesis and VEGF in Cancer
- Endometrial and Cervical Cancer Treatments
- RNA regulation and disease
- PARP inhibition in cancer therapy
- Cancer Immunotherapy and Biomarkers
- Cholangiocarcinoma and Gallbladder Cancer Studies
Queen Mary University of London
2013-2023
Imperial College London
2017-2023
London Cancer
2020
Karolinska Institutet
2006
Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing imprints on the walls of colonic crypts, show that human cells conform one-dimensional neutral drift with a "functional" number five six both normal patients individuals familial adenomatous polyposis (germline APC−/+)....
Significance The organization of cells within human colorectal adenomas, and specifically whether the tumors are maintained by stem cells, is unclear. Furthermore, patterns clonal evolution leading to development a malignant tumor have not been determined. We performed lineage tracing in adenomas using combination nuclear mitochondrial DNA lesions epigenetic markers. Our data identify cell population suggest that new growth intratumor clones occurs infrequently, as steady continual process...
Understanding how life-history strategies influence cancer susceptibility in dinosaurs requires a molecular-level analysis of preserved soft tissues. While previous research has largely focused on skeletal remains, the discovery tissue structures fossils, such as Telmatosaurus transsylvanicus, highlights need for new approach. Paleoproteomics offers transformative opportunity to analyze ancient proteins, revealing evolutionary trade-offs between growth, reproduction, and suppression. This...
<h3>Objective</h3> Barrett9s oesophagus commonly presents as a patchwork of columnar metaplasia with and without goblet cells in the distal oesophagus. The presence metaplastic epithelium on oesophageal biopsy is marker cancer progression risk, but it unclear whether clonal expansion exclusive to cells. <h3>Design</h3> We developed novel method trace ancestry an adenocarcinoma across entire segment. Clonal expansions mucosa were identified using cytochrome c oxidase enzyme histochemistry....
The crypt population in the human intestine is dynamic: crypts can divide to produce two new daughter through a process termed fission, but whether this balanced by second remove crypts, as recently shown mouse models, uncertain. We examined fusion (the of neighbouring fusing into single crypt) occurs colon.
The accumulation of somatic mutations in healthy human tissues has been extensively characterized, but the mutational landscape breast is still poorly understood. Our analysis whole-genome sequencing shows that line with other organs, during reproduction years accumulates age, rate epithelium 15.24 ± 5 mutations/year. Both epithelial and stromal compartments contain breast-specific driver genes, indicative subsequent positive selection. Parity- age-associated differences are evident mammary...
It is widely accepted that the cell of origin breast cancer adult mammary epithelial stem cell; however, demonstrating presence and location tissue cells in human has proved difficult. Furthermore, we do not know clonal architecture normal premalignant epithelium or its cellular hierarchy. Here, use deficiency mitochondrial enzyme cytochrome c oxidase (CCO), typically caused by somatic mutations genome, as a means to perform lineage tracing epithelium. PCR sequencing laser-capture...
While normal human liver is thought to be generally quiescent, clonal hepatocyte expansions have been observed, though neither their cellular source nor expansion dynamics determined. Knowing the cell of origin, and subsequent trajectory within will provide an important basis understand disease-associated dysregulation.
We evaluated the effect of tailoring treatments based on predictions informed by tumor molecular profiles across a range cancers, using data from Caris Life Sciences. These included breast carcinoma, colorectal adenocarcinoma, female genital tract malignancy, lung non-small cell cancer, neuroendocrine tumors, ovarian surface epithelial carcinomas, and urinary cancers. Molecular mostly immunohistochemistry (IHC) DNA sequencing for tumors 841 patients had been previously used to recommend...
// Philip Carter 1 , Costi Alifrangis 2 Biancastella Cereser Pramodh Chandrasinghe 1, 3 Lisa Del Bel Belluz Nina Moderau Fotini Poyia Lee S. Schwartzberg 4 Neha Tabassum Jinrui Wen Jonathan Krell and Justin Stebbing Department of Surgery Cancer, Imperial College, London, UK Oncology, University College Hospital, Surgery, Kelaniya, Sri Lanka West Cancer Center, The Tennessee, Memphis, USA Correspondence to: Carter, email: phil.carter@imperial.ac.uk Keywords: tumor profiling; breast cancer;...
ABSTRACT The accumulation of somatic mutations in the healthy breast throughout life and pregnancy is poorly understood 1–10 . Similarly, mutational landscape both epithelial stromal components mammary gland has not been investigated. Both are relevant for cancer (BC), as interplay between age, pregnancy, risk fully characterized 11 We describe whole genome sequencing analysis compartments from normal breast. show that, a similar way to other organs, burden nulliparous epithelium...
// Philip Carter 1 , Costi Alifrangis 2 Pramodh Chandrasinghe 1, 3, 4 Biancastella Cereser Lisa Del Bel Belluz Cosimo Alex Leo Nina Moderau Neha Tabassum Janindra Warusavitarne Jonathan Krell and Justin Stebbing Department of Surgery Cancer, Imperial College, London, UK Medical Oncology, 3 Surgery, University Kelaniya, Sri Lanka Colorectal St Mark's Hospital, Correspondence to: Carter, email: phil.carter@imperial.ac.uk Keywords: tumor profiling; colorectal adenocarcinoma; cancer treatment...
// Costi Alifrangis 1 , Philip Carter 2 Biancastella Cereser Pramodh Chandrasinghe 2, 3 Lisa Del Bel Belluz Eric Lim 4 Nina Moderau Fotini Poyia Neha Tabassum Hua Zhang 5 Jonathan Krell and Justin Stebbing Department of Oncology, University College Hospital, London, UK Surgery Cancer, Imperial College, Surgery, Kelaniya, Sri Lanka National Heart Lung Institute, Medical Dana-Farber Cancer Boston, MA, USA Correspondence to: Carter, email: phil.carter@imperial.ac.uk Keywords: tumor profiling;...
The majority of human liver research is disease-focused such that far less known cellular dynamics within normal liver. We have leveraged cytochrome c oxidase deficiency as a marker clonal hepatocyte populations in tissues. demonstrate these commonly associate with portal tracts and lineage-trace hepatocytes cholangiocytes, indicating the presence bipotential common ancestor at this niche. also observe rare periportal SOX9+ progenitor candidates our To understand expansion dynamics, we...
<h3>Introduction</h3> Inflammatory bowel disease (IBD) confers a high risk of development colitis-associated colorectal cancer (CACRC) in patients with extensive colitis. It is believed that field effect, resulting from chronic inflammation and clonal outgrowth present ulcerative colitis (UC) patients, this promotes the accumulation protumourigenic clones via increased crypt fission rates. Increased rates may explain mass expansion mutations across whole length very short time period as...
<h3>Introduction</h3> Deficiency in the enzyme cytochrome C oxidase (CCO) has proven to be a versatile marker of clonal population human tissues. CCO is encoded entirely by mitochondrial DNA (mtDNA) and deficiency expression usually attributable mutation mtDNA. CCO-deficient cells are easily detectable two-colour histochemistry. This staining provides means identify patches cells. Subsequent sequencing mtDNA from individual within patch revealing same somatic each cell confirms clonality...
<h3>Introduction</h3> Very little is known about the dynamics and rates of adenoma growth in human colon. Longitudinal barium endoscopic studies demonstrate most smaller adenomas to be static over many years, with a significant proportion even regressing.<sup>1 2</sup> We have recently shown that methylation patterns at CpG loci within non-expressed genes can used infer clonal expansion normal colon.<sup>3</sup> By combining mutational analysis sampling these for crypts adenomas, we aimed...