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The landscape of cancer genomics

Low-cost sequencing has enabled a wide range of cancer genome cohort studies. These studies have resulted in an extensive catalog of the mutational profiles and common oncogene single nucleotide variants (SNVs) present in many cancer types. However, cancer genomes also include large-scale structural variations, such as large insertions, deletions, inversions, duplications, translocations, and gene fusions, all of which can be driver mutations. Most of these variant types have yet to be well-characterized in cancer genomes, leaving gaps in our understanding of how cancer progression and treatment outcomes relate to underlying genotypes1.

 

 

PacBio delivers the most complete view of cancer genome complexity

Single Molecule, Real-Time (SMRT) Sequencing drives discovery in cancer research by providing access to the complete size spectrum of genetic variation in genes, transcripts, and whole genomes. With the Sequel Systems’ exceptionally long reads and high consensus accuracy, scientists have the ability to:

  • Discover hidden biology in cancer samples by fully resolving isoform diversity, including gene fusions, alternative splice sites and retained introns
  • See structural variation in high resolution, including the genomic context of CNVs, exact breakpoints of inversions, insertions, deletions, and translocations, and the full sequence of unstable microsatellite instability biomarkers
  • Directly phase variants across targeted complete genes or large genomic regions, shedding light on the mechanisms of drug resistance
  • Obtain a more faithful view of immune response with full-length immune repertoire sequencing

Research Spotlight: Iso-Seq Method Unravels Activity of Receptors in Prostate Cancer

Targeted SMRT Sequencing of androgen receptor isoforms revealed that the structure of AR-V9 has been previously mischaracterized, omitting a cryptic exon that was thought to appear only in AR-V7.  AR-V7 has been studied as a potential biomarker for drug resistance based on knock-down experiments that have in fact targeted both isoforms, requiring re-interpretation of prior studies. New data suggests AR-V9 may in fact be the more predictive isoform. Explore this research further and learn more about Iso-Seq method.

Kohli, M. et al., 2017. Androgen receptor variant AR-V9 is co-expressed with AR-V7 in prostate cancer metastases and predicts abiraterone resistance. Clinical Cancer Research, ePub ahead of print.

For more information about how SMRT Sequencing can drive your cancer discovery research, contact us.

 

References

  1. Vogelstein, B., et al., (2013) Cancer Genome Landscapes. Science. 339(6127), 1546-1558.
  2. McCombie, W. R. (2015, February) PacBio long read sequencing and structural analysis of a breast cancer cell line, Presented at PacBio Workshop during Advances in Genome Biology and Technology. Marco Island, FL.

 

Selected Resources