Synopsis
Explain how acquired and inherited genomic alterations drive malignant behaviour, distinguish driver from passenger findings, and interpret tumour and germline results without overstating certainty.
- Cancer develops through accumulated alterations that confer selective growth, survival, invasion or immune-evasion advantages; no single universal mutation explains every tumour.
- Oncogenes usually act through gain of function, so one activated allele can promote signalling; examples include RAS pathway activation and ERBB2 amplification.
- Tumour-suppressor genes restrain proliferation, repair DNA or trigger cell death; loss of both functional copies commonly removes that restraint, although mechanisms vary.
- DNA-repair defects increase the rate at which other alterations accumulate and may create treatment biomarkers such as mismatch-repair deficiency or homologous-recombination deficiency.
- Tumour-only testing cannot establish constitutional status; a finding that may be inherited needs consented confirmatory testing in non-tumour tissue through a governed genetics pathway.
- Variant allele fraction, sample purity, copy number and technical limits influence interpretation; a negative panel does not exclude cancer or inherited susceptibility.
- Actionability is context-specific: the same molecular alteration may predict benefit in one tumour type but have uncertain value in another.
- Germline findings require consent, genetics expertise and a plan for relatives, insurance questions, reproductive implications and data governance.
Investigation priorities
Establish lineage and direct focused molecular testing.
Management branches
A cancer diagnosis may need classification, inherited-risk assessment or a treatment biomarker.
- Confirm histological diagnosis, tumour site, stage, available material and the precise decision that a molecular result would change.
- Choose an assay whose validated scope covers the required variant types, and record whether testing is somatic, germline or paired.
- Obtain appropriate consent, including possible inherited implications and the limits of a negative or uncertain result.