Genomic testing is a significant advancement in cancer treatment that moves beyond traditional classification based solely on the organ of origin. This specialized analysis studies the DNA of a person’s cancer cells or their inherited DNA to identify specific alterations, known as variants or mutations. By revealing the unique genetic characteristics of an individual’s disease, this testing provides a molecular blueprint for how the cancer behaves. These insights enable physicians to select therapies that directly target the identified genetic drivers of the tumor, allowing for a highly personalized approach to cancer care.
The Two Core Types of Cancer Genomic Testing
Genomic testing in oncology is divided into two primary categories, each serving a distinct purpose in patient care.
Somatic Testing
Somatic testing analyzes DNA acquired by the tumor cell itself during the cancer’s development. These changes are confined to the tumor tissue and are not passed down through generations. Somatic testing helps oncologists select specific drugs designed to block the pathways activated by these acquired mutations, making the results immediately relevant for treatment planning.
Germline Testing
Germline testing looks for inherited mutations present in every cell of the body since birth. Germline variants, such as those in the BRCA1 and BRCA2 genes, increase a person’s lifetime risk of developing certain cancers. While primarily used for long-term risk management and screening recommendations, germline results can also impact treatment choices.
These two types of testing are complementary, offering different layers of genetic information. Somatic testing focuses on the tumor’s immediate vulnerabilities to guide current therapy decisions. Germline testing addresses the underlying hereditary predisposition, influencing family screening strategies and sometimes providing additional therapeutic options for the patient. In some cases, a mutation found in the tumor via somatic testing may actually be an inherited germline mutation, necessitating follow-up germline testing.
How Genomic Data Guides Treatment Decisions
The results of genomic testing are foundational to the practice of precision oncology, guiding the selection of treatments that are most likely to be effective. Identifying specific biomarkers allows doctors to select targeted therapies, which are drugs designed to interfere with the function of a particular altered protein or pathway identified in the tumor. For example, lung cancers with EGFR mutations can be treated with tyrosine kinase inhibitors, resulting in better outcomes than a general chemotherapy approach. This molecular matching moves away from the one-size-fits-all approach by exploiting the tumor’s unique genetic weaknesses.
Genomic analysis also plays a major role in determining a patient’s potential response to immunotherapy, which harnesses the body’s own immune system to fight cancer. Two genomic markers, microsatellite instability (MSI) and tumor mutational burden (TMB), are commonly assessed for this purpose. Tumors with high MSI or high TMB typically have a large number of mutations, which results in the production of many abnormal proteins that the immune system can more easily recognize as foreign. High TMB is associated with a greater likelihood of response to immune checkpoint inhibitors across several cancer types.
Genomic findings can also influence decisions regarding traditional chemotherapy by identifying variants that predict either sensitivity or resistance to certain agents. Additionally, when standard treatments are not effective, or for patients with rare cancers, genomic data can qualify them for specific clinical trials. These trials often focus on experimental treatments that target a narrow, specific genetic alteration, regardless of where the cancer originated in the body, a concept known as tumor-agnostic treatment.
The Process of Genomic Testing
The process of genomic testing begins with the collection of a biological sample from the patient. For somatic testing, this typically involves obtaining tumor tissue through a surgical procedure or a biopsy. Alternatively, a less invasive liquid biopsy may be performed, which is a blood draw that screens for circulating tumor DNA released from the cancer cells into the bloodstream. Germline testing, which analyzes inherited DNA, is usually performed using a blood sample or a simple cheek swab.
Once the sample reaches the specialized laboratory, the DNA is extracted and prepared for sequencing. Next-generation sequencing (NGS) technology is the standard method used to “read” the DNA code and identify any specific variants, amplifications, or rearrangements. This sequencing step is complex and involves analyzing hundreds of genes simultaneously to create a detailed genetic profile of the tumor or the patient’s inherited code.
The turnaround time, which is the time from sample receipt to the report being issued, can vary depending on the type of test and the lab’s capacity. For complex NGS solid tumor panels, the time frame often ranges from two to four weeks. Delays can occur during the initial steps, such as the time it takes for the tissue to be shipped from the pathology lab to the testing facility.
Understanding and Acting on Test Results
The report generated from genomic testing is a detailed document that requires expert interpretation to translate into a treatment plan. Results are generally categorized into three main types of findings: pathogenic variants, negative findings, and variants of uncertain significance (VUS). A pathogenic variant is a gene change known to increase cancer risk or drive tumor growth, while a negative result indicates no harmful variants were found in the genes tested.
A variant of uncertain significance (VUS) is a change in the DNA for which researchers currently lack enough information to classify as definitively harmful or harmless. Most VUS results are later reclassified as benign, and they typically do not change the patient’s immediate medical care or treatment plan. However, the lab may re-analyze the VUS as new data becomes available, sometimes leading to a reclassification several months or even years later.
Interpreting the full scope of the report requires a multidisciplinary team, including the treating oncologist, a molecular pathologist, and a genetic counselor. Genetic counselors are particularly important for germline results, as they can explain the implications of inherited risk for the patient and guide discussions about cascade testing for at-risk family members. The final treatment recommendation is an integrated decision, utilizing the genomic data alongside the patient’s clinical history and the specific characteristics of their cancer.