Breaking point: the genesis and impact of structural variation in tumours

F1000Res. 2018 Nov 19;7:F1000 Faculty Rev-1814. doi: 10.12688/f1000research.16079.1. eCollection 2018.


Somatic structural variants undoubtedly play important roles in driving tumourigenesis. This is evident despite the substantial technical challenges that remain in accurately detecting structural variants and their breakpoints in tumours and in spite of our incomplete understanding of the impact of structural variants on cellular function. Developments in these areas of research contribute to the ongoing discovery of structural variation with a clear impact on the evolution of the tumour and on the clinical importance to the patient. Recent large whole genome sequencing studies have reinforced our impression of each tumour as a unique combination of mutations but paradoxically have also discovered similar genome-wide patterns of single-nucleotide and structural variation between tumours. Statistical methods have been developed to deconvolute mutation patterns, or signatures, that recur across samples, providing information about the mutagens and repair processes that may be active in a given tumour. These signatures can guide treatment by, for example, highlighting vulnerabilities in a particular tumour to a particular chemotherapy. Thus, although the complete reconstruction of the full evolutionary trajectory of a tumour genome remains currently out of reach, valuable data are already emerging to improve the treatment of cancer.

Keywords: DNA double-strand breaks; Structural variation; cancer; mutational signatures; tumourigenesis; whole genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Transformation, Neoplastic / genetics
  • DNA Breaks, Double-Stranded
  • Genetic Variation*
  • Genome-Wide Association Study
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mutation
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Precision Medicine / methods