Genetic Testing — Analysing Cancer DNA Alterations

Genetic testing refers to the medical laboratory analysis of human chromosomes, genes, or proteins to detect structural alterations associated with disease. In cancer care, testing is divided into two distinct categories: germline testing, which assesses inherited DNA variations present in all cells, and somatic (tumour) testing, which investigates genetic changes acquired exclusively within malignant tissue.

Technological advances such as next-generation sequencing (NGS), polymerase chain reaction (PCR), and fluorescence in situ hybridisation (FISH) allow laboratories to evaluate multiple genes simultaneously. Results identify pathogenic variants that disrupt normal cellular function, such as tumour-suppressor inactivation or oncogene activation, guiding personalised clinical decisions.

Genetic testing provides vital clarity across all stages of oncology care. For healthy individuals with a family history, it clarifies personal risk and enables early screening or prophylactic measures. For individuals diagnosed with cancer, tumour genetic testing identifies molecular alterations that predict how aggressively a cancer might behave and whether it will respond to specific targeted therapies or immunotherapies. This targeted approach spares patients ineffective standard treatments, reduces unnecessary toxicities, and helps optimise overall therapeutic management.

Tests are performed using blood, saliva, bone marrow, or formalin-fixed paraffin-embedded tumour tissue obtained via biopsy or surgery. Circulating tumour DNA can also be analysed through liquid biopsies. Analytical techniques include next-generation sequencing multi-gene panels, Sanger sequencing, immunohistochemistry, and FISH. Testing identifies single nucleotide variants, insertions, deletions, copy number variations, and structural gene fusions.

Genetic testing is widely employed across solid tumours and haematological malignancies. It is standard in breast, ovarian, prostate, and pancreatic cancers to detect homologous recombination defects. In non-small cell lung cancer, testing evaluates driver mutations in EGFR, ALK, and ROS1. It is also central in colorectal and endometrial cancers, melanoma, gastrointestinal stromal tumours, acute leukaemias, and childhood malignancies to identify targetable genomic drivers.

Genetic testing findings dictate the selection of precision oncology therapies. Specific alterations qualify patients for targeted kinase inhibitors, such as osimertinib for EGFR-mutated lung cancer or dabrafenib and trametinib for BRAF-mutant melanoma. Pathogenic BRCA alterations direct the use of PARP inhibitors like olaparib. Demonstrating high microsatellite instability or elevated tumour mutational burden through genetic testing supports treatment with immune checkpoint inhibitors like pembrolizumab.