Cancer genomics — from bench to bedside

The advent of massively parallel sequencing technologies has driven the analysis of cancer genomes at an unprecedented resolution. Sequence data from thousands of patients highlight the distinct sets of driver mutations among patients with the same cancer tissue type, and single-cell sequencing technologies have revealed heterogeneity within the subclones of single tumours as they evolve. Identifying and characterizing these mutations and their diversity is essential for the development of personalized therapies. Next-generation sequencing technologies have also been applied to study the epigenomes and transcriptomes of cancer, thus paving the way for an integrated understanding of cancer pathology.

This collection, which includes articles from Nature Reviews Genetics, Nature Reviews Clinical Oncology and Nature Reviews Cancer, showcases how cancer genomics has informed our understanding of cancer pathogenesis, unravelled potential future therapeutic targets and driven advances that are starting to translate into the clinic. This resource provides a comprehensive bench-to-bedside overview of cancer genomics, which will be useful to researchers and clinicians alike.

Highlights & News

Reviews & Perspectives

  • Nature Reviews Genetics | Review Article

    Although cancer genome sequencing is becoming routine in cancer research, cancer transcriptome profiling through methods such as RNA sequencing (RNA-seq) provides information not only on mutations but also on their functional cellular consequences. This Review discusses how technical and analytical advances in cancer transcriptomics have provided various clinically valuable insights into gene expression signatures, driver gene prioritization, cancer microenvironments, immuno-oncology and prognostic biomarkers.

    • Marcin Cieślik
    •  &  Arul M. Chinnaiyan
  • Nature Reviews Genetics | Review Article

    Cancer immunotherapies are promising strategies for cancer treatment. However, their optimized use will require a comprehensive understanding of the diverse cell types, antigens and genetic variants (both germline and somatic) that comprise the tumour–immune system interface. This Review discusses various bioinformatics tools that process multi-level omics data for insights into tumour–immune cell interactions.

    • Hubert Hackl
    • , Pornpimol Charoentong
    • , Francesca Finotello
    •  &  Zlatko Trajanoski
  • Nature Reviews Genetics | Review Article

    The abundance and heterogeneity of mutations in cancer create challenges for understanding their effects, but such functional characterization will be crucial for optimizing clinical care. In this Review, the authors discuss diverse computational tools and systems biology experimental strategies for elucidating the functional effects of cancer mutations, including consequences on gene regulation, protein structure and local and global perturbations of molecular interaction networks.

    • Song Yi
    • , Shengda Lin
    • , Yongsheng Li
    • , Wei Zhao
    • , Gordon B. Mills
    •  &  Nidhi Sahni
  • Nature Reviews Genetics | Review Article

    The use of phylogenetics in cancer genomics is increasing owing to a growing appreciation of the importance of evolutionary theory to cancer progression. The authors provide guidance on the design and analysis of tumour phylogeny studies by surveying the range of phylogenetic methods and tools available to the cancer researcher and discussing their key applications and the unsolved problems in the field.

    • Russell Schwartz
    •  &  Alejandro A. Schäffer
  • Nature Reviews Cancer | Analysis

    This Analysis article discusses characterization of the kinome in human cancers through genomic, proteomic and functional genomic analyses. In particular, it presents an analysis of cancer genomic data to derive a new census of protein kinase cancer drivers.

    • Emmy D. G. Fleuren
    • , Luxi Zhang
    • , Jianmin Wu
    •  &  Roger J. Daly
  • Nature Reviews Genetics | Review Article

    Genomic analyses of cancer genomes have largely focused on mutations in protein-coding regions, but the functional importance of alterations to non-coding regions is becoming increasingly appreciated through whole-genome sequencing. This Review discusses our current understanding of non-coding sequence variants in cancer — both somatic mutations and germline variants, and their interplay — including their identification, computational and experimental evidence for functional impact, and their diverse mechanisms of action for dysregulating coding genes and non-coding RNAs.

    • Ekta Khurana
    • , Yao Fu
    • , Dimple Chakravarty
    • , Francesca Demichelis
    • , Mark A. Rubin
    •  &  Mark Gerstein