Next Generation Sequencing—Testing Multiple Genetic Markers at Once

Oncologists often look for specific mutations in a person’s tumor biopsy findings because they can represent an important target for specific treatments. Different types of cancer can vary greatly in how often we can expect to find an important mutation. They also differ in the number of potential target mutations we can expect to find.

Until recently, testing for mutations meant running a specific test to look for a single specific mutation, or possibly running several individual tests to look for a few specific targets. Research in personalized medicine has led to a growing number of potentially important target mutations for many cancers. A newer, alternative strategy called next generation sequencing (NGS) allows clinicians to test many genes of a cancer simultaneously. Next generation sequencing can be performed on material from a patient’s tumor that has been biopsied or surgically removed. In some cases, it may be possible to even test a patient’s blood sample for small amounts of tumor DNA that may be shed from the cancer.

Next generation sequencing as a testing strategy has pros and cons compared with an approach of testing for several markers individually.

Pros of NGS:

• It provides the chance to test many genes simultaneously, potentially saving time, money, and tissue if many markers are needed.

• It can provide results not only for the mutations specifically needed, but also can identify new markers that may offer additional treatment options.

• A broader collection of markers may help researchers identify patterns of patient responses that may accelerate research.

Cons of NGS:

• The testing typically takes 2 to 3 weeks for results, while individual tests often take a week or less.

• The cost of testing (typically several thousand dollars) is more than the cost of testing one or a few markers, if no more are needed.

• Some results may be difficult to interpret and lead to treatment decisions that could be harmful to patients compared with more standard treatments.

It is important to ask before any test whether the results will change your care. If the answer is no, doing a test is not clearly valuable, especially if it adds significant costs and consumes limited biopsy tissue. Next generation sequencing is most appropriate for patients who have a cancer in which there are several identified molecular targets that are commonly seen. For other cancers, NGS has a possibility of identifying a mutation that represents a new treatment option, but the odds of this may be very low.

Published Online: May 30, 2019. doi:10.1001/jamaoncol.2019.0453

Conflict of Interest Disclosures: Dr West is a consultant/speaker for and reports personal fees from Ariad/Takeda, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech/Roche, Merck, PharmaMar, Pfizer, Spectrum, and Eli Lilly. No other disclosures are reported.