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Sequence Cancer Variants with Confidence

In order to bring personalized medicine to all patients, cancer researchers need more reliable and comprehensive views of somatic variants of all sizes that drive cancer biology.

 

Uncover Novel Insights in Cancer Biology

Single Molecule, Real-Time (SMRT) Sequencing delivers highly accurate long reads, known as HiFi reads, and uniform coverage needed to access the complete size spectrum of cancer mutations so that you can:

  • Reveal patterns of structural variants to better stratify patients
  • Identify fusion genes and other cancer-specific gene isoforms that may serve as biomarkers
  • Characterize genotypic differences between cohorts that respond differently to treatment by phasing distant SNPs or identifying structural variants
  • Look beyond SNVs and robustly detect all structural variants to reveal novel insights not possible with short-read sequencing

Explore the Range of Applications

Whole Genome Sequencing to assemble complete genomes without the need for a reference to reveal patterns of variants larger and more impactful than SNVs
Structural Variant Detection to identify variants >20 bp that cannot be robustly detected with short-read sequencing, uncovering structural variant hotspots and hidden driver mutations within cohorts at lower cost per sample
Targeting Sequencing to access genomic regions that impact cancer biology in a cost-effective way to further explore variants and identify compound mutations in amplicons up to 20 kb in length
RNA Sequencing to gain a complete view of isoform diversity with the Iso-Seq method by sequencing full-length transcripts up to 10 kb with no assembly required. Or employ a hybrid technology approach to distinguish fusion from non-fusion isoforms

 


 

Phasing PIK3CA mutations with long reads reveals differences in drug response

Only long-read sequencing can phase all PIK3CA double mutations, which are typically located in different protein domains and can be up to 1,790 bp apart in cDNA. Breast cancer patients with double mutations in cis have significantly increased PI3K activity and downstream pathway activation and show enhanced sensitivity to PIK3CA targeted therapy.

Vasan, N., et al. (2019) Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors. Science, 366(6466), 714–723.

Spotlight: Iso-Seq method unravels activity of receptors in prostate cancer

Targeted SMRT Sequencing of androgen receptor (AR) isoforms revealed that the structure of AR-V9 was previously mischaracterized and had omitted a cryptic exon that was thought to appear only in AR-V7. AR-V7 has been identified as a potential biomarker for drug resistance based on knock-down experiments targeting both isoforms. These data suggest AR-V9 may in fact be the more predictive isoform.

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.

Connect with a PacBio scientist to discuss how your cancer research can benefit form highly accurate long-read sequencing.

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