Tumour heterogeneity articles within Nature

Featured

  • Article
    | Open Access

    We uncover key processes of the genomic evolution of small cell lung cancer under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with drug response.

    • Julie George
    • , Lukas Maas
    •  & Roman K. Thomas

  • Article
    | Open Access

    We describe netrin-1 upregulation in a majority of human endometrial carcinomas and demonstrate that netrin-1 blockade, using the anti-netrin-1 antibody NP137, is effective both in a mouse model and in patients with endometrial carcinomas.

    • Philippe A. Cassier
    • , Raul Navaridas
    •  & Patrick Mehlen

  • Article |

    Netrin-1 is upregulated in cancer models that undergo spontaneous epithelial-to-mesenchymal transition, and its targeting blocks the progression of tumour cells to a late mesenchymal state, suggesting possible therapeutic applications.

    • Justine Lengrand
    • , Ievgenia Pastushenko
    •  & Cédric Blanpain

  • Article
    | Open Access

    Micronuclei, which are common features of nuclei in cancer cells, can generate heritable sources of transcriptional suppression, a finding that establishes an inherent relationship between chromosomal instability and variation in chromatin state and gene expression.

    • Stamatis Papathanasiou
    • , Nikos A. Mynhier
    •  & David Pellman

  • Article
    | Open Access

    Missegregated chromosomes that are sequestrated in micronuclei are subject to changes in histone modifications leading to abnormalities in chromatin accessibility that remain long after the chromosomes have been reincorporated into the primary nucleus.

    • Albert S. Agustinus
    • , Duaa Al-Rawi
    •  & Samuel F. Bakhoum

  • Article |

    Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

    • Christopher Abbosh
    • , Alexander M. Frankell
    •  & Charles Swanton

  • Article
    | Open Access

    Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

    • Carlos Martínez-Ruiz
    • , James R. M. Black
    •  & Nicholas McGranahan

  • Article
    | Open Access

    RHOJ regulates epithelial-to-mesenchymal-transition-associated resistance to chemotherapy by enhancing the response to replicative stress and activating the DNA damage response, enabling tumour cells to rapidly repair DNA lesions induced by chemotherapy.

    • Maud Debaugnies
    • , Sara Rodríguez-Acebes
    •  & Cédric Blanpain

  • Article
    | Open Access

    Indole-3-acetic acid (3-IAA), a tryptophan metabolite derived from the gut microbiota, is associated with a better response to chemotherapy in pancreatic ductal adenocarcinoma (PDAC), and dietary interventions could have a role in the treatment of PDAC.

    • Joseph Tintelnot
    • , Yang Xu
    •  & Nicola Gagliani

  • Article
    | Open Access

    Single-cell whole-genome sequencing shows that 'foreground' cell-to-cell structural variation and alterations in copy number are associated with genomic diversity and evolution in triple-negative breast and high-grade serous ovarian cancers.

    • Tyler Funnell
    • , Ciara H. O’Flanagan
    •  & Samuel Aparicio

  • Article
    | Open Access

    A study maps genetic and epigenetic heterogeneity of primary colorectal adenomas and cancers at single-clone resolution through spatial multi-omic profiling of individual glands and adjacent normal tissue.

    • Timon Heide
    • , Jacob Househam
    •  & Andrea Sottoriva

  • Article
    | Open Access

    Intratumour genetic ancestry only infrequently affects gene expression traits and subclonal evolution in colorectal cancer, with most genetic intratumour variation having no detected phenotypic consequence and transcriptional plasticity being widespread within a tumour.

    • Jacob Househam
    • , Timon Heide
    •  & Trevor A. Graham

  • Article |

    Deep whole-genome sequencing of serial blood samples and matched metastatic tissue reveals that circulating tumour DNA profiling enables detailed study of treatment-driven subclone dynamics, epigenomics and genome-wide somatic evolution in metastatic human cancers.

    • Cameron Herberts
    • , Matti Annala
    •  & Alexander W. Wyatt

  • Article |

    Extrachromosomal DNA (ecDNA) congregates in clusters called ecDNA hubs that promote intermolecular interactions between gene-regulatory regions and thereby amplify the expression of oncogenes such as MYC in cancer cell lines.

    • King L. Hung
    • , Kathryn E. Yost
    •  & Howard Y. Chang

  • Article |

    Palmitic acid induces stable transcriptional and chromatin changes that lead to long-term stimulation of metastasis in orthotopic models of cancer through the secretion by tumour-associated Schwann cells of a specialized proregenerative extracellular matrix, the ablation of which inhibits metastasis initiation.

    • Gloria Pascual
    • , Diana Domínguez
    •  & Salvador Aznar Benitah

  • Article |

    Single-cell analysis of genomes from primary human breast tumours and cell lines shows that chromosomal aberrations continue to evolve during primary tumour expansion, resulting in a milieu of subclones within the tumour.

    • Darlan C. Minussi
    • , Michael D. Nicholson
    •  & Nicholas E. Navin

  • Article |

    In mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, malignant progression and metastasis through the activation of a hybrid epithelial-to-mesenchymal transition phenotype.

    • Ievgenia Pastushenko
    • , Federico Mauri
    •  & Cédric Blanpain

  • Article |

    Mutagenic lesions such as those that give rise to cancer frequently segregate—unrepaired—during cell division, resulting in phasing of multiple alleles across generations of daughter cells and consequent tumour heterogeneity.

    • Sarah J. Aitken
    • , Craig J. Anderson
    •  & Martin S. Taylor

  • Article |

    A single-cell, spatially resolved analysis of breast cancer demonstrates the heterogeneity of tumour and stroma tissue and provides a more-detailed method of patient classification than the current histology-based system.

    • Hartland W. Jackson
    • , Jana R. Fischer
    •  & Bernd Bodenmiller

  • Article |

    Populations of KRAS(G12C)-mutant cancer cells can rapidly bypass the effects of treatment with KRAS(G12C) inhibitors because a subset of cells escapes drug-induced quiescence by producing new KRAS(G12C) that is maintained in its active, drug-insensitive state.

    • Jenny Y. Xue
    • , Yulei Zhao
    •  & Piro Lito

  • Article |

    RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

    • Rachel Rosenthal
    • , Elizabeth Larose Cadieux
    •  & Andrew Kidd

  • Article |

    Comparison of multiple lesions from individual pancreases sheds light on how ancestral clones can spread through the ductal system and give rise to precursor lesions, with acquisition of further mutations leading to pancreatic cancer.

    • Alvin P. Makohon-Moore
    • , Karen Matsukuma
    •  & Christine A. Iacobuzio-Donahue

  • Article |

    Epithelial-to-mesenchymal transition in tumour cells occurs through distinct intermediate states, associated with different metastatic potential, cellular properties, gene expression, and chromatin landscape

    • Ievgenia Pastushenko
    • , Audrey Brisebarre
    •  & Cédric Blanpain

  • Article |

    Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

    • Christopher Abbosh
    • , Nicolai J. Birkbak
    •  & Charles Swanton

  • Letter |

    PIK3CA mutations are associated with distinct types of human breast cancers but the cellular origin and mechanisms responsible for this heterogeneity were unclear; here, using a genetic approach in mice, PIK3CA mutations are shown to activate a genetic program directing multiple cell fates in normally lineage-restricted cell types.

    • Alexandra Van Keymeulen
    • , May Yin Lee
    •  & Cédric Blanpain

  • Letter |

    The subclonal composition of human prostate tumours and their metastases has been mapped by whole-genome sequencing, thus establishing the evolutionary trees behind the development and spread of these cancers; an important observation was that metastases could be re-seeded multiple times, and spread from one tumour to another was frequently seen.

    • Gunes Gundem
    • , Peter Van Loo
    •  & G. Steven Bova

  • Article |

    To investigate the role of sub-clonal tumour heterogeneity in cancer progression, a mouse xenograft model was used which revealed that tumour growth can be driven by a minor cell subpopulation by a non-cell-autonomous mechanism, although this minor subpopulation can be outcompeted by faster proliferating competitors.

    • Andriy Marusyk
    • , Doris P. Tabassum
    •  & Kornelia Polyak

  • Article |

    The authors identify pre-leukaemic haematopoietic stem cells (HSCs) in patients with acute myeloid leukaemia; these pre-leukaemic HSCs have the capacity of normal multi-lineage haematopoietic differentiation with a competitive growth advantage over wild-type HSCs, and owing to their persistence may serve as a reservoir for therapeutic resistance and relapse.

    • Liran I. Shlush
    • , Sasan Zandi
    •  & John E. Dick

  • Outlook |

    Leukaemia treatments must eliminate the versatile cells that can bring the cancer back to life years later.

    • Cassandra Willyard

  • Outlook |

    Stem cells from the umbilical cord are among the latest weapons in the fight against leukaemia.

    • Melinda Wenner Moyer

  • Outlook |

    Technologies that rapidly sequence DNA reveal deep genetic diversity both within and among individuals with leukaemia.

    • Sarah DeWeerdt

  • Letter |

    Using genetic lineage tracing, tumour cells are traced in vivo in an unperturbed solid tumour; in a carcinogen-induced papilloma mouse model, cells in these benign lesions are found to mirror the clonal hierarchy organization of normal tissue.

    • Gregory Driessens
    • , Benjamin Beck
    •  & Cédric Blanpain

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