Somatic Mutation — Acquired Genetic Alteration

Somatic mutations arise over an individual's lifetime due to normal errors during cellular replication or from exposure to external mutagens, such as ultraviolet radiation, tobacco smoke, or environmental toxins. These mutations are restricted to the altered cell and the lineage of cells that descend from it, leaving the remainder of the body's tissues genetically unaffected.

When somatic alterations disrupt critical genes that regulate cellular division, survival, or DNA repair—such as oncogenes or tumor suppressor genes—cells may acquire the hallmark capabilities of malignancy. Somatic mutations represent the primary molecular mechanism underpinning the development and evolution of most sporadic cancers.

Somatic mutations play a decisive role in contemporary precision oncology. Identifying specific somatic changes in a patient's tumor allows oncologists to pinpoint targetable weaknesses within the cancer cells. This enables the selection of therapies designed to inhibit mutated proteins directly, sparing healthy tissues from widespread damage. Furthermore, somatic alterations provide prognostic clues and help clinicians monitor disease burden and detect drug resistance.

Somatic mutations are detected by analysing tumor tissue biopsies, surgical specimens, or cell-free circulating tumor DNA (ctDNA) from a liquid biopsy. Next-generation sequencing (NGS), polymerase chain reaction (PCR), and fluorescence in situ hybridisation (FISH) test for alterations in genes such as *EGFR*, *KRAS*, *BRAF*, *PIK3CA*, and *TP53*.

Somatic mutations appear across virtually all human cancers. They are prominently evaluated in non-small cell lung cancer, cutaneous melanoma, colorectal carcinoma, breast cancer, acute myeloid leukaemia, and high-grade serous ovarian cancer, where particular mutations frequently dictate the standard of care.

Detecting actionable somatic mutations directly guides targeted drug selection. For instance, *EGFR* mutations in lung cancer prompt the use of tyrosine kinase inhibitors like osimertinib, while *BRAF* V600E mutations in melanoma indicate treatment with dabrafenib and trametinib. Mutations can also predict resistance to specific agents.