A Closer Look at Cancer—Tumor-Normal Sequencing of DNA Plus RNA Expression

As an oncologist, difficult treatment decisions are a daily reality. By offering a precise and comprehensive molecular tumor profile, GPS Cancer reveal unprecedented insights into the molecular signature of each patient’s cancer. These insights can inform personalized treatment strategies.

Each unique profile includes:

  • Whole genome/exome sequencing of 20,000 genes and 3 billion base pairs
  • Whole transcriptome sequencing of more than 200,000 RNA transcripts
  • Comparison of a patient’s tumor genome to their normal genome and provides pharmacogenomic analysis for potential drug toxicity and/or interactions

GPS Cancer offers molecular insights into therapies that may benefit patients—including FDA-approved therapies and active clinical trials—as well as therapies to which the cancer may be resistant. All GPS Cancer sequencing is performed in CAP-accredited, CLIA-certified labs.

How Precise Is Your Precision Medicine?

Delivering precision cancer care requires precise information. At NantHealth, we believe that looking at tumor DNA isn’t enough. Research reveals that tumor-only sequencing frequently results in false-positives. In many cases, germline mutations are not adequately filtered out.

Likewise, alterations in DNA are sometimes not transcribed into altered RNA or expressed as protein—and therefore may not be viable targets for drug treatment. With GPS Cancer, oncologists gain insights that power personalized care.

25%

25% of cancer patients, on average, will benefit from the offered treatment.1

Why Tumor-Normal Sequencing?

Tumor-normal sequencing can help oncologists avoid inappropriate therapies. Consider the following findings:

2015

John Hopkins – “A tumor-only sequencing approach could not definitively identify germline changes in cancer-predisposing genes that led to additional false-positive findings comprising 31% and 65% of alterations identified in targeted and exome analyses, respectively, including in potentially actionable genes.”2

2017

Moffitt Cancer Center – “Matched tumor/normal mutation detection is more appropriate for applications requiring high precision such as novel mutation detection and mutation signature analysis and remains the optimal approach.”3

2018

NantOmics and NantHealth – With tumor-only sequencing, 29% of lung cancer patients included in the study had at least one false-positive variant in a druggable gene.4

Why RNA Sequencing?

Whole transcriptome (RNA) sequencing may help oncologists avoid inappropriate therapies by confirming genomic alterations that may result in expression of abnormal protein. RNA sequencing provides a quantitative measure of gene expression and identifies gene fusions resulting from genomic translocations.

Advancements in genome (DNA) sequencing have been instrumental in understanding genomic alterations that may drive a patient’s cancer, but genomic sequencing alone is only part of the story.

DNA is the blueprint for RNA. Emerging research shows that alterations in DNA are sometimes not transcribed into altered RNA, or expressed as protein. Likewise, alterations are sometimes introduced at the RNA or protein level that are not detectable at the DNA level.

RNA is the blueprint for protein. To make the most informed treatment decisions, it is essential to understand the impact of genomic alterations on RNA expression and protein.

Statistics

  • In a NantHealth and NantOmics study comparing tumor-only to tumor-normal sequencing in 621 patients across 30 different cancer types, “filtering for common SNPs still resulted in as high as 48% false-positive variant calling.”5
  • 74% reduction in risk of death or disease progression in melanoma patients with BRAF V600E mutation treated with targeted therapy vs. standard of care.5
  • 52% reduction in tumor recurrence when Herceptin is used in combination with chemotherapy vs. chemotherapy alone.5
  • $604M annual savings when Panitumamab or Cetuximab is limited to colorectal cancer patients whose KRAS gene is not mutated.5

The Era of Precision Medicine is Here

We’re here to help you give your patients better treatments—and potentially better chances. With Precision Insights, you can:


1 Cancer Principles and Practice of Oncology. 6th Edition DeVita, et al. Lippincott Williams and Wilkins

2 CITATION: Rabizadeh S., Garner C., Sanborn J. Zachary, Benz S. C., Reddy S., Soon-Shiong P. Comprehensive genomic transcriptomic tumor-normal gene panel analysis for enhanced precision in patients with lung cancer. Oncotarget. 2018; 9: 19223-19232.

3 Teer JK et al. Evaluating somatic tumor mutation detection without matched normal samples. Human Genomics. 2017;11:22.

4 Personalized genomic analyses for cancer mutation discovery and interpretation. Jones S, Anagnostou V, Lytle K, Parpart-Li S, Nesselbush M, Riley DR, Shukla M, Chesnick B, Kadan M, Papp E, Galens KG, Murphy D, Zhang T, Kann L, Sausen M, Angiuoli SV, Diaz LA Jr, Velculescu VE. Sci Transl Med. 2015 Apr 15;7(283):283ra53. doi: 10.1126/scitranslmed.aaa7161

CITATION: 5 RABIZADEH ET AL J Clin Oncol 33, 2015 (suppl; abstr 11093)