Kerstin Thol
A5054971786- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Ovarian cancer diagnosis and treatment
- Renal cell carcinoma treatment
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- Immunotherapy and Immune Responses
- Genomics and Phylogenetic Studies
- Molecular Biology Techniques and Applications
- Cellular Mechanics and Interactions
- Ferroptosis and cancer prognosis
- Immune Cell Function and Interaction
- Microtubule and mitosis dynamics
- Hippo pathway signaling and YAP/TAZ
- Cell Adhesion Molecules Research
- Cancer-related Molecular Pathways
- Radiomics and Machine Learning in Medical Imaging
- Single-cell and spatial transcriptomics
- Prostate Cancer Treatment and Research
- T-cell and B-cell Immunology
- MRI in cancer diagnosis
- Body Contouring and Surgery
- Cholangiocarcinoma and Gallbladder Cancer Studies
CRUK Lung Cancer Centre of Excellence
2021-2025
University College London
2021-2025
London Cancer
2021-2025
Cancer Research UK
2021-2025
Imperial College London
2019-2023
Turku Centre for Computer Science
2021-2022
Turku Centre for Biotechnology
2019-2022
University of Turku
2019-2022
Royal London Hospital
2022
Åbo Akademi University
2021-2022
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 Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, applications are constrained by the sensitivity of clinically validated ctDNA approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically for ultrasensitive at 1–3 ppm with 99.9% specificity. Through an analysis 171 patients lung cancer from TRACERx study, we detected pre-operatively within 81% adenocarcinoma (LUAD), including 53% those...
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,...
Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer
Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer. During invasion, the encapsulating DCIS basement membrane (BM) compromised, and tumor cells invade surrounding stroma. The mechanisms that regulate functional epithelial BMs vivo are poorly understood. Myosin-X (MYO10) filopodia-inducing protein associated with metastasis poor clinical outcome invasive cancer (IBC). We identify elevated MYO10 expression human IBC, this suggests links disease progression. promotes...
Limited evidence exists on the impact of spatial and temporal heterogeneity high-grade serous ovarian cancer (HGSOC) tumor evolution, clinical outcomes, surgical operability. We perform systematic multi-site mapping at presentation matched relapse from 49 high-tumor-burden patients, operated up front. From SNP array-derived copy-number data, we categorize dendrograms representing clonal evolution as sympodial or dichotomous, noting most chemo-resistant patients favor simpler evolution. Three...
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...
Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with increased mortality among patients cancer. CHIP mutations high variant-allele frequencies can be detected in tumors, a phenomenon we term tumor-infiltrating clonal (TI-CH). The frequency TI-CH and its effect on tumor evolution are unclear. We characterized 421 early-stage non-small-cell lung cancer (NSCLC) from the TRACERx study 49,351 MSK-IMPACT pan-cancer cohort. studied association survival...
Abstract Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves a lethal state. To characterize the intra-patient evolutionary relationships of metastases that evade we perform genome-wide copy number profiling and bespoke approaches targeting androgen receptor (AR) on 167 regions from 11 organs harvested post-mortem 10 men who died cancer. We identify diverse patient-unique alterations clustering around AR in every patient with evidence independent...
Adhesion formation contributes to postoperative complications in abdominal and gynaecological surgery. Thus far, the prevention treatment strategies have focused on mechanical barriers solid liquid form, but these methods are not routine use. As autologous fat grafting has become popular of hypertrophic scars because its immunomodulatory effects, we postulated that could also prevent peritoneal adhesion through similar mechanisms. This was a control versus intervention study evaluate effect...
Abstract Extrachromosomal DNA (ecDNA) is emerging as a major contributor to cancer drug resistance and poor outcome in many types. To understand the underlying genetic mutational processes associated with ecDNA formation presence, we conducted an analysis of whole-genome sequencing data from 14,778 patients representing 39 tumor types Genomics England cohort. Our findings revealed focal amplifications driven by 17.1% samples, exhibiting varying frequencies across tissues. Notably,...
<h3>Introduction/Background</h3> High-grade serous ovarian cancer (HGSOC) is typified by high degrees of genomic instability and heterogeneity, with the majority patients eventually acquiring resistance to platinum chemotherapy. Matching best treatment options remains challenging due diverse mechanisms limited effective predictive biomarkers. This study aims understand extent intra-tumoural heterogeneity (ITH) in advanced stage HGSOC, how this changes over time at relapse, define link...
Abstract Background: Genomic intra-tumor heterogeneity (ITH) drives tumor evolution, leading to immune evasion and resistance therapy. Emerging evidence implicates the transcriptome as a source of important variation that impacts phenotype. Here, we perform genomic-transcriptomic analysis transcriptomic diversity upon 941 regions taken from 357 TRACERx non-small cell lung cancers (NSCLC) across primary metastatic disease subjected high-depth bulk DNA RNA sequencing, well 91 tumor-adjacent...
Abstract Checkpoint inhibitors (CPI), ameliorate the anti-tumour response by blocking inhibitory immune checkpoint receptors, and have revolutionised treatment of advanced cancers. However, prediction is suboptimal, there remains a strong reliance on tumour mutation burden (TMB). Studies to date are limited whole exome sequencing (WES), with no data yet reported utility genome (WGS) in pan-cancer cohort. Here we report cohort 318 tumour/normal genomes from Genomics England 100,000 Genomes...
Abstract High-grade serous ovarian cancer (HGSOC) is the most common subtype of cancer, accounting for more than 70% all epithelial cancers. It characterized by high degrees genomic instability and heterogeneity, with majority patients eventually acquiring resistance to platinum chemotherapy. The diversity in platinum-resistance mechanisms limited effective predictive biomarkers mean delivering best treatment options patient tumor remains challenging. purpose this study understand extent...