Browsing by author "Graham, Trevor"

Now showing items 1-20 of 38

    • A Big Bang model of human colorectal tumor growth. 

      Sottoriva, A; Kang, H; Ma, Z; Graham, TA; Salomon, MP; et al. (NATURE PUBLISHING GROUP, 2015-03-01)
      What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion ...

    • Between-region genetic divergence reflects the mode and tempo of tumor evolution. 

      Sun, R; Hu, Z; Sottoriva, A; Graham, TA; Harpak, A; et al. (NATURE PUBLISHING GROUP, 2017-06-05)
      Given the implications of tumor dynamics for precision medicine, there is a need to systematically characterize the mode of evolution across diverse solid tumor types. In particular, methods to infer the role of natural ...

    • 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 ...

    • Catch my drift? Making sense of genomic intra-tumour heterogeneity. 

      Sottoriva, A; Barnes, CP; Graham, TA (ELSEVIER, 2017-04-01)
      The cancer genome is shaped by three components of the evolutionary process: mutation, selection and drift. While many studies have focused on the first two components, the role of drift in cancer evolution has received ...

    • 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 ...

    • Clinical trial designs for evaluating and exploiting cancer evolution. 

      Ingles Garces, AH; Porta, N; Graham, TA; Banerji, U (ELSEVIER SCI LTD, 2023-07-01)
      The evolution of drug-resistant cell subpopulations causes cancer treatment failure. Current preclinical evidence shows that it is possible to model herding of clonal evolution and collateral sensitivity where an initial ...

    • 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 ...

    • Evolutionary dynamics of neoantigens in growing tumors. 

      Lakatos, E; Williams, MJ; Schenck, RO; Cross, WCH; Househam, J; et al. (NATURE PORTFOLIO, 2020-10-01)
      Cancers accumulate mutations that lead to neoantigens, novel peptides that elicit an immune response, and consequently undergo evolutionary selection. Here we establish how negative selection shapes the clonality of ...

    • 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 ...

    • Germline MBD4 deficiency causes a multi-tumor predisposition syndrome. 

      Palles, C; West, HD; Chew, E; Galavotti, S; Flensburg, C; et al. (CELL PRESS, 2022-05-05)
      We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic ...

    • 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 ...

    • 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 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 ...