Detecting Mutations in Normal Tissue: Now What?

Maurie Markman, MD


February 04, 2019

This transcript has been edited for clarity.

Hello. I'm Dr Maurie Markman from Cancer Treatment Centers of America in Philadelphia. I wanted to briefly discuss an extremely interesting and quite provocative paper which recently appeared in Science, entitled "Somatic Mutant Clones Colonize the Human Esophagus With Age."[1]

This group of investigators looked at the normal esophagus in nine individuals aged 20-75 years to look for mutations. Quite surprisingly, they found a very large incidence of what would be considered cancer-related mutations within the esophagus, with the number of mutant clones (abnormalities) increasing with age.

In fact, they noted that "the prevalence of NOTCH1 mutations in the normal esophagus was several times higher than in esophageal cancers." This paper is obviously quite provocative, leading to the question: What time within the development of cancers do these mutations actually occur within normal tissue—in this case, the normal esophageal epithelium?

It also raises the very important and potentially concerning question of the apparent ability to detect precancerous lesions, for example, with liquid tumor biopsies. The idea has been touted that one could potentially find cancers before they develop by looking at the blood, looking for mutations, and then looking for the actual cancer.

If, in fact, it's true, as shown here, that these mutations are very common, they may have nothing to do with the development of cancer, at least in an individual's lifetime. These mutations could lead to the search for cancers that don't exist, invasive procedures that are not necessary, and potential serious morbidity or even mortality for the patient.

There are no definitive answers. But this paper in a top-notch medical journal, looking at a limited number of patients who don't have cancer, raises the question of the ability of perhaps looking for these mutations too early in the natural history of potential cancer. And what would that mean?

Obviously, further follow-up of this report is critical, but it is a very important paper that challenges certain notions, existing notions, of when these mutations develop within cancers and their relationship to normal physiology and normal biology and the aging process.

I encourage you to read this very interesting paper, which just appeared in Science. Thank you for your attention.


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