Tumour profiling

Genetic testing is clinically relevant for the following indications, including but not limited to:

• Patients with advanced or metastatic solid cancers being considered for systemic therapy
• Advanced non-squamous non-small-cell lung, prostate, colorectal, ovarian or breast cancer, for which multigene tumour profiling is recommended
• Tumours in which microsatellite instability or mismatch-repair status serves as a predictive biomarker
• Solid tumours in which a tumour-agnostic target such as an NTRK gene fusion may be present⁶

Testing is typically requested by the treating medical oncologists, pathologists, and molecular tumour boards.

Molecular tumour profiling is considered when treatment selection in advanced solid cancer depends on the tumour’s genomic make-up. Detecting actionable alterations and predictive biomarkers supports clinical decision making, matching patients to targeted treatment options and informing prognosis.

A somatic alteration of strong or potential clinical significance identifies a driver or biomarker and, where actionable, a treatment target. Other alterations might be of unknown clinical significance. In some cases, no actionable alteration can be detected. A clinically relevant alteration cannot, however, be entirely excluded, as it may lie outside the assay’s coverage or fall below the detection limit at low tumour cell content. Especially when alterations with high variant allele frequencies are detected in tumour tissue, somatic and germline origin cannot reliably be distinguished. A suspected germline variant requires confirmation from a constitutional sample. Each detected alteration is classified for clinical significance and actionability according to .

When an actionable alteration is identified, it can direct the patient to a matched therapy and support molecular tumour board discussion. Predictive biomarkers such as microsatellite instability, or MGMT promoter methylation in glioblastoma, refine treatment choice and inform prognosis. A finding suggestive of an inherited predisposition can be discussed with the care team; confirmation requires a separate germline analysis, and a negative tumour result does not exclude one.

Testing uses DNA-based multi-gene panels and RNA-based gene fusion panels and . Fragment length analysis for and promoter methylation assays are applied where indicated.