Somatic testing is a specialized laboratory method that analyzes the genetic material within a patient’s cells to look for acquired changes in their DNA. This testing focuses exclusively on alterations that have developed over a person’s lifetime, rather than genetic information inherited from their parents. It is primarily performed in oncology, often referred to as tumor or biomarker testing. The goal of this analysis is to profile the unique genetic landscape of a disease, such as cancer, to inform treatment planning. Identifying specific changes in the tumor’s DNA helps doctors predict how the disease might respond to different therapeutic approaches.
Somatic Versus Germline Alterations
The distinction between somatic and germline alterations represents a fundamental concept in genetic testing. A somatic alteration is a genetic change that is acquired after conception, meaning it is not present in all the cells of the body. These alterations occur sporadically in specific cells, such as those that form a tumor, and cannot be passed down to one’s children.
A germline alteration, by contrast, is an inherited genetic change present in the egg or sperm cells, which means it exists in every cell of the body from the moment of conception. Germline mutations are transmissible from parent to child and often relate to an increased risk of developing certain diseases, including cancer. Somatic testing, therefore, isolates the tumor’s DNA to exclusively study these acquired, non-heritable errors that are actively driving the disease.
Clinical Utility in Treatment Selection
The results of somatic testing are instrumental in precision oncology, guiding the selection of therapies tailored to a patient’s specific tumor profile. By identifying particular genetic targets, also known as biomarkers, physicians can match patients to drugs designed to disrupt the cancer’s unique growth mechanism. For example, in lung cancer, identifying an EGFR mutation or an ALK gene fusion can direct treatment toward specific targeted kinase inhibitors that block the function of those altered proteins.
Somatic testing is also used to determine a tumor’s eligibility for immunotherapy, a type of treatment that harnesses the patient’s immune system to fight cancer. The presence of high microsatellite instability (MSI-H) or a high tumor mutational burden (TMB) suggests that the tumor may respond favorably to immune checkpoint inhibitors. Identifying these biomarkers allows for the application of effective treatments. Furthermore, somatic testing provides prognostic information, offering insights into the likely aggressiveness of the disease and its potential for recurrence. Serial testing can also monitor the tumor’s evolution, detecting the emergence of new mutations that confer resistance to a current drug, which then signals the need for a change in treatment strategy.
Testing Procedures and Sample Types
Somatic testing requires a sample of the tumor tissue or its genetic material shed into the bloodstream. The traditional method is a solid tissue biopsy, where a small piece of the tumor is surgically removed or extracted using a needle. This tissue sample allows for a comprehensive analysis of the tumor’s architecture and the genetic alterations present within the cells. A key advantage of solid tissue is that it can also be used for additional tests, such as immunohistochemistry, which looks for specific proteins on the cell surface.
An alternative, less invasive approach is the liquid biopsy, which analyzes circulating tumor DNA (ctDNA) fragments found in a standard blood sample. These ctDNA fragments carry the same genetic mutations as the original tumor. Liquid biopsies are beneficial when a tumor is inaccessible for a physical biopsy or when a patient’s condition makes a surgical procedure too risky. Both sample types are then analyzed using advanced methods, most commonly next-generation sequencing (NGS), a high-throughput technology that simultaneously reads the sequence of hundreds of genes to identify subtle DNA changes.
Interpreting Somatic Test Outcomes
Somatic test outcomes are classified based on the clinical significance of the detected genetic alterations, guiding the next steps in patient care. The most important findings are categorized as “actionable mutations,” which are genetic changes linked to an available, approved, or highly recommended therapy. For instance, a BRAF V600E mutation in melanoma is considered actionable because a targeted inhibitor drug exists to treat cancers with that specific alteration. These clear-cut results immediately inform treatment selection.
A more complex finding is the “variant of uncertain significance” (VUS), which is a genetic change whose effect on the tumor is not yet known or clearly defined. A VUS is an uninformative result that cannot be interpreted as benign or disease-causing based on current scientific evidence. Specialized teams, often called multidisciplinary tumor boards, review the full spectrum of results, including actionable mutations and resistance mutations, which indicate how a tumor has genetically evolved to evade a previous treatment. This collaborative interpretation ensures that the genetic data is linked to the best possible therapy plan for the patient.