Browsing by author "Sottoriva, Andrea"
Now showing items 21-40 of 53
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Identification of neutral tumor evolution across cancer types.
Williams, MJ; Werner, B; Barnes, CP; Graham, TA; Sottoriva, A (NATURE PUBLISHING GROUP, 2016-03-01)Despite extraordinary efforts to profile cancer genomes, interpreting the vast amount of genomic data in the light of cancer evolution remains challenging. Here we demonstrate that neutral tumor evolution results in a ... -
Immune selection determines tumor antigenicity and influences response to checkpoint inhibitors.
Zapata, L; Caravagna, G; Williams, MJ; Lakatos, E; AbdulJabbar, K; et al. (NATURE PORTFOLIO, 2023-03-01)In cancer, evolutionary forces select for clones that evade the immune system. Here we analyzed >10,000 primary tumors and 356 immune-checkpoint-treated metastases using immune dN/dS, the ratio of nonsynonymous to synonymous ... -
Immunosuppressive niche engineering at the onset of human colorectal cancer.
Gatenbee, CD; Baker, A-M; Schenck, RO; Strobl, M; West, J; et al. (NATURE PORTFOLIO, 2022-04-04)The evolutionary dynamics of tumor initiation remain undetermined, and the interplay between neoplastic cells and the immune system is hypothesized to be critical in transformation. Colorectal cancer (CRC) presents a unique ... -
Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics.
Sottoriva, A; Spiteri, I; Piccirillo, SGM; Touloumis, A; Collins, VP; et al. (NATL ACAD SCIENCES, 2013-03-05)Glioblastoma (GB) is the most common and aggressive primary brain malignancy, with poor prognosis and a lack of effective therapeutic options. Accumulating evidence suggests that intratumor heterogeneity likely is the key ... -
Longitudinal Liquid Biopsy and Mathematical Modeling of Clonal Evolution Forecast Time to Treatment Failure in the PROSPECT-C Phase II Colorectal Cancer Clinical Trial.
Khan, KH; Cunningham, D; Werner, B; Vlachogiannis, G; Spiteri, I; et al. (AMER ASSOC CANCER RESEARCH, 2018-08-30)Sequential profiling of plasma cell-free DNA (cfDNA) holds immense promise for early detection of patient progression. However, how to exploit the predictive power of cfDNA as a liquid biopsy in the clinic remains unclear. ... -
Many private mutations originate from the first few divisions of a human colorectal adenoma.
Kang, H; Salomon, MP; Sottoriva, A; Zhao, J; Toy, M; et al. (WILEY, 2015-11-01)Intratumoural mutational heterogeneity (ITH) or the presence of different private mutations in different parts of the same tumour is commonly observed in human tumours. The mechanisms generating such ITH are uncertain. ... -
Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking.
Cresswell, GD; Nichol, D; Spiteri, I; Tari, H; Zapata, L; et al. (NATURE PORTFOLIO, 2020-03-27)Circulating tumour DNA (ctDNA) allows tracking of the evolution of human cancers at high resolution, overcoming many limitations of tissue biopsies. However, exploiting ctDNA to determine how a patient's cancer is evolving ... -
Measuring cancer evolution from the genome.
Graham, TA; Sottoriva, A (WILEY-BLACKWELL, 2017-01-01)The temporal dynamics of cancer evolution remain elusive, because it is impractical to longitudinally observe cancers unperturbed by treatment. Consequently, our knowledge of how cancers grow largely derives from inferences ... -
Measuring Clonal Evolution in Cancer with Genomics.
Williams, MJ; Sottoriva, A; Graham, TA (ANNUAL REVIEWS, 2019-08-31)Cancers originate from somatic cells in the human body that have accumulated genetic alterations. These mutations modify the phenotype of the cells, allowing them to escape the homeostatic regulation that maintains normal ... -
Measuring single cell divisions in human tissues from multi-region sequencing data.
Werner, B; Case, J; Williams, MJ; Chkhaidze, K; Temko, D; et al. (NATURE PUBLISHING GROUP, 2020-02-25)Both normal tissue development and cancer growth are driven by a branching process of cell division and mutation accumulation that leads to intra-tissue genetic heterogeneity. However, quantifying somatic evolution in ... -
Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios.
Williams, MJ; Zapata, L; Werner, B; Barnes, CP; Sottoriva, A; et al. (ELIFE SCIENCES PUBLICATIONS LTD, 2020-03-30)The distribution of fitness effects (DFE) defines how new mutations spread through an evolving population. The ratio of non-synonymous to synonymous mutations (dN/dS) has become a popular method to detect selection in ... -
Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity.
Heindl, A; Khan, AM; Rodrigues, DN; Eason, K; Sadanandam, A; et al. (NATURE RESEARCH, 2018-09-25)How tumor microenvironmental forces shape plasticity of cancer cell morphology is poorly understood. Here, we conduct automated histology image and spatial statistical analyses in 514 high grade serous ovarian samples to ... -
Modeling evolutionary dynamics of epigenetic mutations in hierarchically organized tumors.
Sottoriva, A; Vermeulen, L; Tavaré, S (PUBLIC LIBRARY SCIENCE, 2011-05-05)The cancer stem cell (CSC) concept is a highly debated topic in cancer research. While experimental evidence in favor of the cancer stem cell theory is apparently abundant, the results are often criticized as being difficult ... -
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
Vlachogiannis, G; Hedayat, S; Vatsiou, A; Jamin, Y; Fernández-Mateos, J; et al. (AMER ASSOC ADVANCEMENT SCIENCE, 2018-02-23)Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from ... -
Phenotypic plasticity and genetic control in colorectal cancer evolution.
Househam, J; Heide, T; Cresswell, GD; Spiteri, I; Kimberley, C; et al. (NATURE PORTFOLIO, 2022-11-24)Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity1. The interplay of these biological processes and their respective contributions to tumour evolution remain ... -
Prediction of Benefit from Checkpoint Inhibitors in Mismatch Repair Deficient Metastatic Colorectal Cancer: Role of Tumor Infiltrating Lymphocytes.
Loupakis, F; Depetris, I; Biason, P; Intini, R; Prete, AA; et al. (WILEY, 2020-01-22)BACKGROUND: Immunotherapy with immune checkpoint inhibitors (ICIs) is highly effective in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC); however, specific predictive biomarkers are lacking. ... -
Quantification of spatial subclonal interactions enhancing the invasive phenotype of pediatric glioma.
Tari, H; Kessler, K; Trahearn, N; Werner, B; Vinci, M; et al. (CELL PRESS, 2022-08-30)Diffuse midline gliomas (DMGs) are highly aggressive, incurable childhood brain tumors. They present a clinical challenge due to many factors, including heterogeneity and diffuse infiltration, complicating disease management. ... -
Quantification of subclonal selection in cancer from bulk sequencing data.
Williams, MJ; Werner, B; Heide, T; Curtis, C; Barnes, CP; et al. (NATURE PUBLISHING GROUP, 2018-05-28)Subclonal architectures are prevalent across cancer types. However, the temporal evolutionary dynamics that produce tumor subclones remain unknown. Here we measure clone dynamics in human cancers by using computational ... -
Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns.
Bollen, Y; Stelloo, E; van Leenen, P; van den Bos, M; Ponsioen, B; et al. (NATURE PORTFOLIO, 2021-08-01)Central to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at ... -
Reply to 'Neutral tumor evolution?'
Heide, T; Zapata, L; Williams, MJ; Werner, B; Caravagna, G; et al. (2018-12)