Breaking point: the genesis and impact of structural variation in tumours
Open Access
- 19 November 2018
- journal article
- review article
- Published by F1000 Research Ltd in F1000Research
- Vol. 7, 1814
- https://doi.org/10.12688/f1000research.16079.1
Abstract
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.Funding Information
- UKRI Innovation Fellowship
- UK Medical Research Council
This publication has 100 references indexed in Scilit:
- Signatures of mutational processes in human cancerNature, 2013
- Diverse Mechanisms of Somatic Structural Variations in Human Cancer GenomesCell, 2013
- Deciphering Signatures of Mutational Processes Operative in Human CancerCell Reports, 2013
- Mutational Processes Molding the Genomes of 21 Breast CancersCell, 2012
- Genome Sequencing of Pediatric Medulloblastoma Links Catastrophic DNA Rearrangements with TP53 MutationsCell, 2012
- Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer DevelopmentCell, 2011
- International network of cancer genome projectsNature, 2010
- The landscape of somatic copy-number alteration across human cancersNature, 2010
- Nucleotide-resolution analysis of structural variants using BreakSeq and a breakpoint libraryNature Biotechnology, 2010
- Complex landscapes of somatic rearrangement in human breast cancer genomesNature, 2009