Cancer genomics

  • Article
    | Open Access

    A biologically informed, interpretable deep learning model has been developed to evaluate molecular drivers of resistance to cancer treatment, predict clinical outcomes and guide hypotheses on disease progression.

    • Haitham A. Elmarakeby
    • , Justin Hwang
    •  & Eliezer M. Van Allen
  • Article |

    Laser-capture microdissection and mini-bulk exome sequencing are combined to analyse somatic mutations in morphologically normal tissues from nine organs from five donors, revealing variation in mutation burdens, mutational signatures and clonal expansions.

    • Ruoyan Li
    • , Lin Di
    •  & Chen Wu
  • Article |

    The authors report the mutational landscape of 29 cell types from microdissected biopsies from 19 organs and explore the mechanisms underlying mutation rates in normal tissues.

    • Luiza Moore
    • , Alex Cagan
    •  & Raheleh Rahbari
  • Article |

    A new computational approach to in silico mutagenesis screening allow comprehensive mapping of cancer driver mutations.

    • Ferran Muiños
    • , Francisco Martínez-Jiménez
    •  & Nuria Lopez-Bigas
  • Article |

    NanoSeq is used to detect mutations in single DNA molecules and analyses show that mutational processes that are independent of cell division are important contributors to somatic mutagenesis.

    • Federico Abascal
    • , Luke M. R. Harvey
    •  & Iñigo Martincorena
  • Article |

    Aneuploid cancer cell lines show increased dependence on the spindle assembly complex (SAC); initially they are resistant to SAC perturbations, but over time they accumulate chromosomal aberrations that impair their fitness.

    • Yael Cohen-Sharir
    • , James M. McFarland
    •  & Uri Ben-David
  • Article |

    Mutations in histone H1 induce the remodelling of chromatin architecture to a more relaxed state, which leads to malignant transformation through changes in histone modifications and the expression of stem cell genes.

    • Nevin Yusufova
    • , Andreas Kloetgen
    •  & Ari M. Melnick
  • Article |

    A method in which pooled barcoded human cancer cell lines are injected into a mouse xenograft model enables simultaneous mapping of the metastatic potential of multiple cell lines, and shows that breast cancer cells that metastasize to the brain have altered lipid metabolism.

    • Xin Jin
    • , Zelalem Demere
    •  & Todd R. Golub
  • 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 |

    Whole-genome sequencing of normal human endometrial glands shows that most are clonal cell populations and frequently carry cancer driver mutations that occur early in life, and that parity has a protective effect.

    • Luiza Moore
    • , Daniel Leongamornlert
    •  & Michael R. Stratton
  • Article |

    Genomic, transcriptomic and DNA methylation data from tissue samples from 208 Chinese patients with prostate cancer define the landscape of alterations in this population, and comparison with data from Western cohorts suggests that the disease may stratify into different molecular subtypes.

    • Jing Li
    • , Chuanliang Xu
    •  & Yinghao Sun
  • Article |

    Circulating tumour DNA in blood is analysed to identify genomic features that distinguish early-stage lung cancer patients from risk-matched controls, and these are integrated into a machine-learning method for blood-based lung cancer screening.

    • Jacob J. Chabon
    • , Emily G. Hamilton
    •  & Maximilian Diehn
  • Article
    | Open Access

    Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

    • Moritz Gerstung
    • , Clemency Jolly
    •  & Peter Van Loo
  • Article
    | Open Access

    Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

    • Claudia Calabrese
    • , Natalie R. Davidson
    •  & Zemin Zhang
  • Article
    | Open Access

    Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

    • Yilong Li
    • , Nicola D. Roberts
    •  & Peter J. Campbell
  • Article |

    Whole-genome sequencing of normal bronchial epithelium from 16 individuals shows that tobacco smoking increases genomic heterogeneity, mutational burden and driver mutations, whereas stopping smoking promotes replenishment of the epithelium with near-normal cells.

    • Kenichi Yoshida
    • , Kate H. C. Gowers
    •  & Peter J. Campbell
  • Article |

    Analyses of primary and relapse samples of embryonal tumours with multilayered rosettes provide insights into the molecular mechanisms that underlie the development and opportunities for the treatment of this deadly disease.

    • Sander Lambo
    • , Susanne N. Gröbner
    •  & Marcel Kool
  • Article |

    A genome-wide association study of mosaic loss of chromosome Y (LOY) in UK Biobank participants identifies 156 genetic determinants of LOY, showing that LOY is associated with cancer and non-haematological health outcomes.

    • Deborah J. Thompson
    • , Giulio Genovese
    •  & John R. B. Perry
  • Article |

    The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure

    • Floris P. Barthel
    • , Kevin C. Johnson
    •  & Roel G. W. Verhaak
  • Article
    | Open Access

    The mutational landscape of metastatic cancer genomes is analysed in a large-scale, pan-cancer study of metastatic solid tumours that includes whole-genome sequencing of 2,520 tumour–normal tissue pairs.

    • Peter Priestley
    • , Jonathan Baber
    •  & Edwin Cuppen
  • Article |

    Whole-genome sequencing of liver microdissections from five healthy individuals and nine with cirrhosis demonstrates the effects of liver disease on the genome, including increased rates of mutation, complex structural variation and different mutational signatures.

    • Simon F. Brunner
    • , Nicola D. Roberts
    •  & Peter J. Campbell
  • Letter |

    A range of SF3B1 mutations promote tumorigenesis through the repression of BRD9, a core component of the non-canonical BAF complex, and correcting BRD9 mis-splicing in these SF3B1-mutant cells suppresses tumour growth.

    • Daichi Inoue
    • , Guo-Liang Chew
    •  & Robert K. Bradley
  • Letter |

    Analysis of more than 17,000 tumours suggests that the contribution of germline and somatic mutations in the BRCA1 and BRCA2 genes to oncogenesis depends on tumour lineage.

    • Philip Jonsson
    • , Chaitanya Bandlamudi
    •  & Barry S. Taylor
  • Article |

    Profiling of over 38,000 CD34+ cells from patients with CALR-mutated myeloproliferative neoplasms, using the ‘Genotyping of Transcriptomes’ procedure, reveals that the transcriptional output of these mutations depends upon native cell identity.

    • Anna S. Nam
    • , Kyu-Tae Kim
    •  & Dan A. Landau
  • Article |

    Analysis of growth dynamics in a dataset from 107 patients with chronic lymphocytic leukaemia (CLL) reveals both exponential and logistic patterns of growth, which are associated with differences in genetic attributes and clinical outcomes.

    • Michaela Gruber
    • , Ivana Bozic
    •  & Catherine J. Wu
  • Letter |

    Analyses of fragmentation patterns of cell-free DNA in the blood of patients with cancer and healthy individuals using a machine learning algorithm provide a proof-of principle approach for the early detection and screening of human cancer.

    • Stephen Cristiano
    • , Alessandro Leal
    •  & Victor E. Velculescu
  • Letter |

    A single-cell approach is used to follow the heritable stochastic changes to DNA methylation that occur in primary chronic lymphocytic leukaemia and healthy B cells, allowing the tracing of cell lineage histories and evolution during treatment with ibrutinib.

    • Federico Gaiti
    • , Ronan Chaligne
    •  & Dan A. Landau
  • Article |

    The original Cancer Cell Line Encyclopedia (CCLE) is expanded with deeper characterization of over 1,000 cell lines, including genomic, transcriptomic, and proteomic data, and integration with drug-sensitivity and gene-dependency data.

    • Mahmoud Ghandi
    • , Franklin W. Huang
    •  & William R. Sellers
  • Article |

    In a screen of 324 human cancer cell lines and utilising a systematic target prioritization framework, the Werner syndrome ATP-dependent helicase is shown to be a synthetic lethal target in tumours from multiple cancer types with microsatellite instability, providing a new target for cancer drug development.

    • Fiona M. Behan
    • , Francesco Iorio
    •  & Mathew J. Garnett
  • Letter |

    Depletion of the DNA helicase WRN induced double-stranded DNA breaks, and promoted apoptosis and cell cycle arrest selectively in cancers with microsatellite instability, indicating that WRN is a promising drug target for the treatment of these cancers.

    • Edmond M. Chan
    • , Tsukasa Shibue
    •  & Adam J. Bass
  • 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