Structural variation & cancer: top 7 things to read right now

Somatic mutations are the driving force behind cancer development, and structural variations (SVs) are more and more being recognised as an important class of these mutations. The detection of SVs is challenged, though, by existing short-read sequencing technologies, and extensive recent research has explored the role of long-read sequencing in characterising causative and prognostic rearrangements in cancer.

We’ve picked out 7 of the best articles to read right now, at the forefront of cancer research using nanopore sequencing.

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  1. PUBLICATION: Improved structural variant interpretation for hereditary cancer susceptibility using long-read sequencing

Germline variants in cancer predisposition genes are estimated to underlie 5 to 10% of all cancers, but this estimation is based primarily on single nucleotide changes and small indels, as structural variants have been difficult to detect using existing technologies. My Linh Thibodeau and team hypothesise that this could mean the role of SVs in hereditary cancer predisposition is likely underestimated, and are researching methods of detection that could have important implications in future carrier screening and prophylactic interventions.

Read the full article | 30 min read

  1. BLOG: Copy number variation analysis from plasma: is it feasible using nanopore sequencing?

Filippo Martignano describes characterisation of the genetic features of each individual patient’s tumour as the “pivotal step” in precision oncology, and the ability to do this from bodily fluids instead of invasive sampling processes is essential for practical implementation. Sequencing-based analysis of cell-free DNA is currently limited only to large research hospitals and institutions, so Filippo’s team are exploring methods to detect copy number variation (and in future other aberrations) in a rapid, simple way that could be more widely distributed. This blog summarises their feasibility studies performed so far, and describes their next steps towards opening up genetic analysis of circulating tumour DNA to a wider audience.

Read the full blog | 10 min read

  1. BIOINFORMATICS: Precise characterisation of somatic structural variations and mobile element insertions with nanomonsv

Detection of variants in cancer samples presents a unique computational challenge, as complex combinations of alterations can occur at varying, and often low, frequency levels. Accurate description of somatic structural variants can help in understanding the mechanisms of cancer development, as well as the functional consequences of particular mutations. In this pre-print, Shiraishi et al demonstrate their computational approach to this problem, achieving breakpoint resolution of SVs at the single nucleotide level.

Read the full article | 30 min read

  1. PUBLICATION: Rapid identification of genomic structural variations with nanopore sequencing enables blood-based cancer monitoring

Liquid biopsy approaches not only provide a non-invasive method of cancer investigation, but also represent a viable option for ongoing monitoring of cancer progression, remission or potential recurrence. Using a low-coverage genome sketching approach on cancer samples, Jose Espejo Valle-Inclan and team rapidly identified somatic structural variants in circulating tumour DNA, and combined this with digital PCR to retrospectively monitor treatment response in metastatic prostate cancer patients.

Read the full article | 30 min read

  1. PUBLICATION: Partner independent fusion gene detection by multiplexed CRISPR-Cas9 enrichment and long read nanopore sequencing

Recent studies suggest that up to 16% of cancers could be driven by fusion genes – hybrid genes formed of two previously independent genes brought into proximity usually by translocation, interstitial deletion or chromosomal inversion. Some cancers are characterised by distinct pairings of two genes, but others don’t display such strong associations, and so detection methods that aren’t dependent on knowledge of both partners or exact breakpoint location are important for more universal analyses.  Christina Stangl and team made use of a PCR-free, Cas9-based enrichment strategy for this purpose, selecting for DNA containing a fusion, and developed their own analysis pipeline to support this detection.

Read the full article | 30 min read

  1. WHITE PAPER: The promise of nanopore sequencing for clinical and cancer research

Widespread adoption of sequencing into clinical research has led to unprecedented insights into the role of genomics in human health. The most highly adopted technologies in these settings are based on short-read sequencing, which relies on large, costly instrumentation and short sequencing read lengths. In this white paper, case studies are examined on the part long-read sequencing will play in the evolution of clinical research and potentially testing.

Read the full white paper | 30 min read

  1. PUBLICATION: Nanopore sequencing enables comprehensive transposable element epigenomic profiling

Transposable elements are a common and influential feature of genomic architecture, impacting many aspects of human health, including cancers. Their regulation is determined by a number of mechanisms, the most prominent of which is thought to be CpG methylation, which normally requires additional steps such as bisulphite conversion to fully identify. Adam Ewing and his group utilised PCR-free whole genome sequencing to detect both transposable elements and methylation in a single dataset, making detection of both transposition and regulation possible simultaneously.

Read the full article | 30 min read


Want to know more about calling structural variation from nanopore data? You can find out more about the practicalities in our guide “Getting started with structural variation detection” available to read here.