Comprehensive Tumour NGS Profiling

What It Measures

• Somatic mutations across 300–500 cancer-relevant genes
• Tumour Mutational Burden (TMB) — predictive of immunotherapy (pembrolizumab) response
• Microsatellite Instability (MSI-H/MSS) — predicts checkpoint inhibitor benefit
• NTRK, RET, ALK, ROS1 gene fusions — targetable with approved drugs across tumour types
• KRAS G12C — targetable with Sotorasib (Lumakras) in lung and other cancers
• BRCA1/2 somatic mutations — predicts PARP inhibitor (olaparib) response
• HER2 amplification, EGFR mutations, PIK3CA mutations
• PD-L1 expression (in combined IHC panels)
• Homologous recombination deficiency (HRD) score

How It Works

Tumour tissue from a biopsy or surgical specimen (FFPE blocks or fresh frozen tissue) is sent to the laboratory. DNA and RNA are extracted and sequenced across a comprehensive gene panel using next-generation sequencing. Bioinformatics pipelines compare tumour DNA to matched normal DNA (or a reference population) to identify somatic mutations. Results are reviewed by molecular pathologists and reported with FDA-approved drug matches, clinical trial matches, and evidence levels for each finding.

• All patients with metastatic or advanced cancer — guideline-recommended
• Patients whose cancer has progressed after standard first-line therapy
• Rare tumour types where standard treatments are limited
• Patients seeking clinical trial eligibility (trials often require specific biomarkers)
• Younger cancer patients where germline contribution needs exclusion
• Any case where targeted therapy decision-making would benefit from full genomic context

Comprehensive tumour NGS profiling is now guideline-standard for multiple cancer types including NSCLC, melanoma, colorectal (MSI), breast (HR/HER2), and all metastatic solid tumours (NCCN 2024). The TAPUR study demonstrated that genomic matching improved outcomes in 28% of heavily pre-treated patients across 19 cancer types. Foundation Medicine's FoundationOne CDx is FDA-approved as a companion diagnostic for 15+ drugs. The NCI-MATCH trial showed molecular matching produced responses in rare cancers where histology-based treatment had failed. TMB-high status is now an FDA-approved biomarker for pembrolizumab across all solid tumours.

This list is not exhaustive. Ask your oncologist or integrative physician for locally available options.

• Requires adequate tumour tissue — insufficient material is a common failure mode
• FFPE fixation can introduce artefactual mutations — lab quality controls are critical
• Many mutations identified are Variants of Uncertain Significance (VUS) with no actionable implication
• Tumour heterogeneity means one biopsy site may not represent the full mutational landscape
• A 'targetable' mutation in the report does not guarantee drug response in that patient
• Requires specialist molecular tumour board interpretation — not for self-interpretation