Historically, many cancer tests searched for a limited number of DNA genes (fewer than 50 typically). Broader sequencing was simply too slow and expensive. Today, advanced testing can examine roughly 21,000 genes while analyzing RNA too, revealing cancer-driving alterations that narrower tests may miss. If your tumor's driver falls outside the test's scope, a potentially treatable finding can go undetected.
Studies comparing narrow, hotspot-only panels with broader testing have found that broadening the panel turns up an actionable result for many patients who had none on the narrow panel, and identifies matched therapies more often. Broad testing also keeps working over time. In one analysis of more than 47,000 tumors, the share of patients whose existing results pointed to a standard-of-care targeted treatment rose from about 9 percent in 2017 to about 32 percent in 2022, with no new testing, simply because more treatments had been approved in the meantime. Medical groups increasingly recommend broader testing, especially for advanced-stage cancer.
This gap matters most for advanced or previously treated cancers, where resistance mutations and rarer alterations with targeted treatments available are common but often sit outside a standard hotspot panel.
How broadly a test reads your tumor can also change how certain markers are scored. Independent studies have found that smaller gene panels and whole-exome sequencing often disagree when measuring tumor mutational burden, a marker used to decide whether immunotherapy is likely to help. Panels that read less than about one million bases of DNA carry enough error to put some patients on the wrong side of the cutoff. In one analysis of patients receiving the immunotherapy pembrolizumab, the patients that whole-exome scoring called high, and smaller panels called low, lived about five months longer than the group scored the other way around. If this marker matters in your case, ask your oncologist how it was measured.
For Example
A patient with advanced lung cancer has a small hotspot panel come back with nothing to target, so treatment defaults to standard chemotherapy without much to go on. Broader testing of that same tumor turns up a less common alteration with an approved targeted therapy, letting the care team build a treatment plan around what is actually driving that patient's cancer.
Questions To Ask Your Oncologist
- How many genes does this test look at, and does it include RNA?
- If this test finds nothing actionable, would broader testing be worth doing?