Genetic and Genomic Testing

Genetic and genomic testing in cancer care analyzes genetic alterations in tumor cells or blood to better understand the molecular features of a cancer. The results may help with diagnosis, classification, risk assessment, and treatment selection.

In blood cancers, testing can identify gene mutations, gene fusions, and chromosomal abnormalities that help classify diseases such as leukemia, lymphoma, and multiple myeloma, assess prognosis, and guide treatment. In solid tumors, genomic testing is often used to identify biomarkers that may help guide targeted therapy, immunotherapy, or other treatment options.

Tumor genomic testing usually looks for acquired changes in cancer cells and is different from germline genetic testing, which evaluates inherited cancer risk.

The type of genetic or genomic testing needed varies by cancer type, stage, and the purpose of testing.

For example, acute myeloid leukemia may be tested for alterations such as FLT3 and NPM1, while chronic myeloid leukemia requires testing for BCR::ABL1. Some patients with lung cancer are tested for alterations such as EGFR, ALK, and ROS1. Broader multigene testing may also be considered for some advanced or recurrent solid tumors to identify potentially actionable biomarkers.

Germline genetic testing may be recommended in selected situations, such as cancer diagnosed at a young age, a significant family history of cancer, or tumor features that suggest an inherited cancer predisposition.

Cancer genomic testing can use different types of samples, including tumor tissue, bone marrow, and peripheral blood. Solid tumor testing commonly uses tissue obtained through surgery or biopsy, while blood cancers may be tested using bone marrow or peripheral blood samples.

Testing methods may include PCR, fluorescence in situ hybridization (FISH), chromosome analysis, and next-generation sequencing (NGS). Each method detects different types and ranges of genetic alterations, so the appropriate test depends on the specific cancer and clinical question.

For some solid tumors, circulating tumor DNA (ctDNA) from a blood sample can be used as a liquid biopsy when tumor tissue is difficult to obtain. Results need to be interpreted in the appropriate clinical context.

Genomic test results need to be interpreted together with the cancer type, stage, pathology, previous treatments, and other clinical information. Finding a genetic alteration does not necessarily mean that an approved targeted therapy is available or that a patient will benefit from a particular treatment.

A negative result also does not completely rule out a relevant alteration. Results can be affected by sample quality, tumor content, and the testing method used. Because the molecular features of a cancer may change as the disease progresses or develops treatment resistance, repeat tissue or blood testing may sometimes be considered.

If testing identifies an alteration that may be inherited, additional germline testing and genetic counseling may be needed to determine whether it represents an inherited genetic change.