Browsing Molecular Pathology by author "Graham, Trevor"

Now showing items 1-20 of 22

    • Cancer associated fibroblast FAK regulates malignant cell metabolism. 

      Demircioglu, F; Wang, J; Candido, J; Costa, ASH; Casado, P; et al. (NATURE PUBLISHING GROUP, 2020-03-10)
      Emerging evidence suggests that cancer cell metabolism can be regulated by cancer-associated fibroblasts (CAFs), but the mechanisms are poorly defined. Here we show that CAFs regulate malignant cell metabolism through ...

    • Cell Competition in Carcinogenesis. 

      Madan, E; Palma, AM; Vudatha, V; Trevino, JG; Natarajan, KN; et al. (AMER ASSOC CANCER RESEARCH, 2022-12-16)
      The majority of human cancers evolve over time through the stepwise accumulation of somatic mutations followed by clonal selection akin to Darwinian evolution. However, the in-depth mechanisms that govern clonal dynamics ...

    • Classifying the evolutionary and ecological features of neoplasms. 

      Maley, CC; Aktipis, A; Graham, TA; Sottoriva, A; Boddy, AM; et al. (NATURE PUBLISHING GROUP, 2017-10-01)
      Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive ...

    • Colorectal cancer residual disease at maximal response to EGFR blockade displays a druggable Paneth cell-like phenotype. 

      Lupo, B; Sassi, F; Pinnelli, M; Galimi, F; Zanella, ER; et al. (AMER ASSOC ADVANCEMENT SCIENCE, 2020-08-05)
      Blockade of epidermal growth factor receptor (EGFR) causes tumor regression in some patients with metastatic colorectal cancer (mCRC). However, residual disease reservoirs typically remain even after maximal response to ...

    • Crypt fusion as a homeostatic mechanism in the human colon. 

      Baker, A-M; Gabbutt, C; Williams, MJ; Cereser, B; Jawad, N; et al. (BMJ PUBLISHING GROUP, 2019-11-01)
      OBJECTIVE: The crypt population in the human intestine is dynamic: crypts can divide to produce two new daughter crypts through a process termed crypt fission, but whether this is balanced by a second process to remove ...

    • Detecting repeated cancer evolution from multi-region tumor sequencing data. 

      Caravagna, G; Giarratano, Y; Ramazzotti, D; Tomlinson, I; Graham, TA; et al. (NATURE PUBLISHING GROUP, 2018-08-31)
      Recurrent successions of genomic changes, both within and between patients, reflect repeated evolutionary processes that are valuable for the anticipation of cancer progression. Multi-region sequencing allows the temporal ...

    • First passage time analysis of spatial mutation patterns reveals sub-clonal evolutionary dynamics in colorectal cancer. 

      Haughey, MJ; Bassolas, A; Sousa, S; Baker, A-M; Graham, TA; et al. (PUBLIC LIBRARY SCIENCE, 2023-03-01)
      The signature of early cancer dynamics on the spatial arrangement of tumour cells is poorly understood, and yet could encode information about how sub-clones grew within the expanding tumour. Novel methods of quantifying ...

    • FUME-TCRseq enables sensitive and accurate sequencing of the T-cell receptor from limited input of degraded RNA. 

      Baker, A-M; Nageswaran, G; Nenclares, P; Ronel, T; Smith, K; et al. (American Association for Cancer Research (AACR), 2024-03-14)
      Genomic analysis of the T-cell receptor (TCR) reveals the strength, breadth, and clonal dynamics of the adaptive immune response to pathogens or cancer. The diversity of the TCR repertoire, however, means that sequencing ...

    • Genomic landscape and clonal architecture of mouse oral squamous cell carcinomas dictate tumour ecology. 

      Sequeira, I; Rashid, M; Tomás, IM; Williams, MJ; Graham, TA; et al. (NATURE PORTFOLIO, 2020-11-09)
      To establish whether 4-nitroquinoline N-oxide-induced carcinogenesis mirrors the heterogeneity of human oral squamous cell carcinoma (OSCC), we have performed genomic analysis of mouse tongue lesions. The mutational ...

    • 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 ...

    • Lineage tracing in human tissues. 

      Gabbutt, C; Wright, NA; Baker, A-M; Shibata, D; Graham, TA (WILEY, 2022-05-05)
      The dynamical process of cell division that underpins homeostasis in the human body cannot be directly observed in vivo, but instead is measurable from the pattern of somatic genetic or epigenetic mutations that accrue in ...

    • 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 ...

    • The mutational signatures of formalin fixation on the human genome. 

      Guo, Q; Lakatos, E; Bakir, IA; Curtius, K; Graham, TA; et al. (NATURE PORTFOLIO, 2022-09-06)
      Clinical archives of patient material near-exclusively consist of formalin-fixed and paraffin-embedded (FFPE) blocks. The ability to precisely characterise mutational signatures from FFPE-derived DNA has tremendous ...

    • 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 ...

    • 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 ...

    • Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution. 

      Baker, A-M; Huang, W; Wang, X-MM; Jansen, M; Ma, X-J; et al. (NATURE PUBLISHING GROUP, 2017-12-08)
      Intra-tumor heterogeneity (ITH) is a major underlying cause of therapy resistance and disease recurrence, and is a read-out of tumor growth. Current genetic ITH analysis methods do not preserve spatial context and may not ...

    • Spatially constrained tumour growth affects the patterns of clonal selection and neutral drift in cancer genomic data. 

      Chkhaidze, K; Heide, T; Werner, B; Williams, MJ; Huang, W; et al. (PUBLIC LIBRARY SCIENCE, 2019-07-29)
      Quantification of the effect of spatial tumour sampling on the patterns of mutations detected in next-generation sequencing data is largely lacking. Here we use a spatial stochastic cellular automaton model of tumour growth ...

    • Subclonal reconstruction of tumors by using machine learning and population genetics. 

      Caravagna, G; Heide, T; Williams, MJ; Zapata, L; Nichol, D; et al. (NATURE PUBLISHING GROUP, 2020-09-01)
      Most cancer genomic data are generated from bulk samples composed of mixtures of cancer subpopulations, as well as normal cells. Subclonal reconstruction methods based on machine learning aim to separate those subpopulations ...

    • The co-evolution of the genome and epigenome in colorectal cancer 

      Sottoriva, A; Heide, T; Cresswell, G; Spiteri, I; Lynn, C; et al. (2021-07-12)
      Colorectal malignancies are a leading cause of cancer death. Despite large-scale genomic efforts, DNA mutations do not fully explain malignant evolution. Here we study the co-evolution of the genome and epigenome of ...