Next Generation Sequencing (NGS), which is becoming more widely known as Comprehensive Genomic Profiling by Massively Parallel Sequencing (CGP), will significantly contribute to targeted therapies and precision medicine. We provide a brief snapshot of what NGS/CGP is, how it works, where it is being used, the potential difficulties and what’s on the horizon.
What is Next Generation Sequencing?
Next Generation Sequencing (NGS) is becoming more widely known as Comprehensive Genomic Profiling by Massively Parallel Sequencing (CGP)
NGS/CGP testing will significantly contribute to targeted therapy
Multiple genes are analysed simultaneously so there is the potential to detect all mutations in a patient specimen
The four steps of NGS/CGP are:
A machine reads the DNA and provides a sequence of bases. Sequences from patient samples are compared to known references
Where is NGS/CGP being incorporated?
NGS/CGP uses the same methodology to screen for a variety of cancer genes (a panel)
NGS/CGP is being adopted for NSCLC due to the complexity of the driver and resistance mutation tied to therapy options (Figure 1)
NCCN and ESMO guidelines support broad molecular testing (e.g., NGS/CGP) in non-small cell lung cancer (NSCLC)
Figure 1. Mutations driving NSCLC.
What is the current situation with NGS/CGP in labs?
There are two distinct groups of NGS/CGP panels emerging:
Smaller, ~50 gene panels that are built with known actionable biomarkers
Larger, 500+ gene panels to whole exome sequencing
NGS/CGP is largely centralized to large commercial reference labs and academic institutions
Many US labs are adopting NGS/CGP – Illumina and ThermoFisher platforms dominate the clinical space (Figure 2)
EGFR and ALK, along with ROS1 and MET, are commonly part of lung NGS/CGP cancer panels
Some laboratories do not include ALK in panels as they have a more cost-efficient test validated for ALK
Figure 2. NGS market share of top 20 NGS somatic mutation panel offering laboratories. (*Market share is based on a blended mix of Medicare datasets of different biomarkers performed by NGS.)
Difficulties associated with NGS/CGP
Turnaround times are lengthy as NGS/CGP is a more complex and labour intensive methodology compared with single gene tests and may exceed the therapeutic window, e.g., in AML
NGS/CGP diffusion is currently limited to key cancer and reference labs
Reflex strategy may be required to account for low quality or quantity of DNA
Coverage of sequencing panels still varies between insurers and may be restricted
What’s coming up?
The requirement for BRAF testing and sequencing of other genes in the test panel will be a major driver for the adoption of NGS/CGP
Platform suppliers and the FDA are striving for NGS to become part of therapeutic labels
Leading pharma and diagnostic companies will embrace NGS/CGP to address key treatment and support their own pipeline and strategic goals