FAQ: Large scale genomic tumor testing
Frequently asked questions about large panel genomic tumor testing
Q: What is large panel genomic tumor testing?
A: Biomarker testing includes DNA, RNA, and proteins. Large panel genomic tumor testing aims to specifically detect DNA changes, or variants, in tumor cells to aid in diagnosis, prognosis and identification of targeted treatments. “Large panel” refers to the dozens or even hundreds of genetic variants that are analyzed, with implications for many different cancer types. These variants are in genes with associated FDA-approved treatments, or in genes where off-label treatments are available or in context of clinical trials. While large panel genomic tumor testing is relatively new and changing quickly, oncologists have used targeted genomic testing to guide therapeutic decisions for some time now, testing for single, specific genomic variants in solid tumors, such as EGFR variants in lung cancer. As our understanding of genomic drivers of carcinogenesis has grown, so has the library of useful tumor biomarkers. At the same time, the power and efficiency of genomic testing has increased. Together, this has enabled the use of large panel genomic tumor testing, where a patient’s cancer is interrogated for hundreds or even thousands of variants.
Q: For which patients is large panel genomic tumor testing appropriate?
A: Currently, patients with metastatic or advanced cancer are recommended to undergo large panel biomarker testing if more than one biomarker-linked therapy is approved for the patient’s disease (ASCO 2022). Oncologists may choose to use it for patients with advanced cancers whose disease has progressed during standard treatments, or for those with particularly aggressive or metastatic disease, while others may use it with newly diagnosed patients to assess all treatment options.
Q: For which patients may large panel genomic tumor testing not be useful?
A: Large panel genomic tumor testing may not be useful for all patients. It may not be useful for certain types of cancer that have a well-established standard of care treatment. It also may not be indicated for early-stage cancers, as the results may not have significant impact on treatment decisions.
Q: What are the benefits?
A: Large panel genomic tumor testing may identify opportunities to treat the patient with therapies targeted to specific genomic variants driving cancer growth. These targeted therapies may be FDA approved for the cancer type, approved for other cancer types, or are available through clinical trials. It may also provide diagnostic or prognostic information which could be used to inform treatment decisions.
Q: What are limitations?
A: Not all patients whose tumors are tested will have a variant that changes treatment. Results may not show the complete molecular picture of the cancer and some treatment options may be missed. This is because tumors are often heterogeneous, and a biopsy sample only represents a subset of the cancer. Also, the genetic makeup of a tumor changes over time as the cancer cells divide. Variants detected in the original tumor biopsy often differ from those found in metastasized sites, and it may not be possible to obtain biopsies from all sites.
Even those who do may not have a change in treatment. Evidence supporting efficacy of targeted treatments in different cancer types is still growing and may not support use of a particular treatment even when a variant is present. There may be other therapeutic approaches that are more likely to be effective. Additionally, patients may have limited access to treatment options identified by testing, due to a lack of an appropriate clinical trial nearby or lack of insurance coverage.
Q: How is the testing done?
A: Most commonly, CLIA-certified labs extract DNA from a tumor biopsy or blood sample for large panel genomic tumor testing. Using next-generation sequencing (NGS), the lab identifies variants in the genes on the panel. Labs differ in which genes they include in their tests, but most include those involved in pathways that affect the development or growth of cancer.
Q: What can results tell you?
A: Large panel genomic tumor testing is typically done to assess a patient’s likelihood to respond to targeted therapies. Testing can help determine if the patient’s tumor or tested metastases carry any of these targetable genomic variants. In some cases, results may also inform prognosis or origin of the cancer if it has been difficult to determine otherwise.
Q: Can large panel genomic tumor testing identify individuals with hereditary cancer syndromes?
A: In some cases. Genetic testing for hereditary cancer syndromes (e.g., Lynch syndrome, hereditary breast and ovarian cancer syndrome) typically involves testing a blood or oral sample to identify germline pathogenic variants that are present in every cell of the body and can be passed from parent to child. Germline variants in these cancer susceptibility genes increase a person’s chance of developing certain cancers in their lifetime and may also provide additional options for targeted treatment.
Not all types of large panel genomic tumor tests can determine whether a variant is present only in cancer cells (somatic) or in all cells (germline). If the oncologist suspects a variant might be in the germline, further work-up by a genetic specialist or additional, dedicated germline testing may be indicated.
Not all variants associated with hereditary cancer syndromes may be included on large scale genomic tumor tests. Even when the variants are included on the panel, they may not be reported or may be undetectable. It is always important to assess the patient’s personal and family history of cancer to determine whether further evaluation by a genetic expert is warranted, regardless of the results from testing.
Q: What have patient experiences been with large panel genomic tumor testing so far?
A: Cancer patients consistently report a high willingness and interest but may not understand much about genomics or the implications for their care. Managing patient expectations should be part of the conversation when considering large scale genomic tumor testing. See Facilitating shared decision making about genomic tumor testing for more information on discussing options with patients.
Exploring Cancer Biomarker Testing(CME / CNE). Learn about benefits, limitations, and challenges of using cancer biomarker testing.
Interpreting Results from Somatic Cancer Panels (CME / CNE). Practice interpreting results from large panel somatic testing within a patient-specific context.
Choosing the Best Genomic Tumor Test (CME / CNE). Learn about the benefits and limitations of different genomic tumor test options for patients with cancer and how to determine the best test for each patient.
Facilitating shared decision making about genomic tumor testing. Supports clinicians when communicating about the process, benefits, and limitations of genomic tumor testing.
Indications for Germline Testing in Cancer Patients. Provides a quick reference about the factors to consider when determining the appropriateness of germline testing.
This resource was developed as part of the Maine Cancer Genomics Initiative (MCGI) and is supported by The Harold Alfond Foundation and The Jackson Laboratory.
Updated May 2023