PATHCHAT Edition No. 80
Published: August 2022
Please contact your local Ampath pathologist for more information.
Author:
- Dr. Michael Bromfield
Introduction
✅ Cancer as a Genomic Disease
- Cancer remains a leading cause of death worldwide, with nearly 10 million deaths in 2020.
- Malignancies arise due to the accumulation of genetic mutations that drive uncontrolled cell growth.
- Advances in next-generation sequencing (NGS) have revolutionized oncology, allowing precision-based treatment strategies.
- Genomic profiling helps refine disease prognosis and select the most appropriate therapies based on tumour molecular characteristics.
📌 NGS technology enables a deeper understanding of the genetic mutations underlying tumour development and progression.
The Benefits of Next-Generation Sequencing (NGS) in Cancer Diagnosis
✅ Advantages of NGS Over Traditional Molecular Techniques
- NGS detects multiple genetic alterations simultaneously, improving efficiency and cost-effectiveness.
- Can analyze various mutation types in a single test, including:
- Single nucleotide variants (SNVs).
- Small insertions/deletions (indels).
- Copy number variations (amplifications or deletions).
- Gene fusions and rearrangements.
- Requires minimal DNA input (as little as 10 ng), preserving biopsy samples for further testing.
- Detects genomic variants even at very low levels within tumour cells.
- Enables faster, individualized treatment decisions.
📌 NGS provides a comprehensive tumour profile that enhances diagnostic accuracy and treatment selection.
The Value of OPANGS in Precision Medicine
✅ What is OPANGS?
- OPANGS (Oncomine™ Precision Assay) is a cutting-edge NGS-based test for analysing multiple solid tumour malignancies.
- Simultaneously detects key genetic alterations in major cancer types.
✅ Cancers Commonly Tested Using OPANGS:
- Non-small cell lung cancer (NSCLC):
- EGFR mutations.
- ALK fusions.
- BRAF mutations.
- ROS1, RET, KRAS G12C, and MET alterations.
- Breast and gastric cancer:
- HER2 (ERBB2) amplification.
- Colorectal cancer:
- KRAS, NRAS, and BRAF mutations.
- Melanoma:
- BRAF mutations.
- Cholangiocarcinoma:
- FGFR2 alterations.
📌 Identifying tumour-specific mutations enables precision-targeted therapy selection, reducing ineffective treatments and minimizing adverse effects.
Fusion Detection & Tumour-Agnostic Therapy
✅ The Role of RNA Sequencing in Fusion Detection
- RNA sequencing improves detection of fusion events, including:
- ALK, ROS1, RET, MET, FGFR2, and NUTM1 rearrangements.
- NGS can identify treatment-resistant fusion variants that influence therapy selection.
✅ Tumour-Agnostic Therapy Targets Identified by OPANGS:
- NTRK gene fusions:
- Detected in various solid tumours, including sarcomas and gliomas.
- Patients with NTRK-positive tumours may benefit from larotrectinib (Vitrakvi®) or entrectinib (Rozlytrek®).
- Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR):
- Indicates eligibility for pembrolizumab (Keytruda®) in colorectal cancer and other solid tumours.
- Tumour mutational burden-high (TMB-H):
- Predicts response to immunotherapy in various malignancies.
📌 NGS-based fusion detection enables the identification of tumour-agnostic treatment options for patients with actionable gene rearrangements.
Liquid Biopsy & OPANGS
✅ What is Liquid Biopsy?
- A minimally invasive technique to detect oncogenic mutations using circulating tumour DNA (ctDNA) from blood samples.
- Enables real-time molecular profiling of cancer without requiring a tissue biopsy.
✅ Advantages of Liquid Biopsy:
- Less invasive compared to tissue biopsies.
- Allows early detection of tumour progression and metastatic relapse.
- Facilitates real-time monitoring of therapy response and emergence of resistance mutations.
- Can be repeated multiple times to assess tumour evolution.
- Provides a more comprehensive representation of intra-tumoural heterogeneity.
- May reduce the overall cost of managing metastatic disease by avoiding repeat surgical biopsies.
📌 Liquid biopsy serves as a complementary tool in cancer management, but tissue biopsy remains the gold standard for initial diagnosis.
Key Takeaways for Clinicians
✅ Precision oncology relies on genetic profiling to guide targeted cancer therapy.
✅ NGS enables comprehensive mutation detection, improving diagnostic accuracy and treatment selection.
✅ The OPANGS panel allows simultaneous testing of multiple tumour types in a single assay.
✅ Fusion detection through RNA sequencing helps identify patients eligible for tumour-agnostic therapies.
✅ Liquid biopsy provides a non-invasive approach for real-time monitoring of cancer progression.
📌 Advancements in NGS and liquid biopsy are transforming cancer diagnostics, making precision medicine more accessible and effective.
For More Information on NGS-Based Testing
✅ Contact the Ampath NGS Laboratory:
- Email: ngs@ampath.co.za
- Genetic Counselling Appointments: geneticsclinic@ampath.co.za
📌 Ampath’s comprehensive genomic testing services provide cutting-edge solutions for precision oncology.