Methylated DNA may be key to whole-body cancer screening

Volume 4, Issue 3, 2015


GI research leads Mayo Clinic investigators to new targets in cancer detection.

Photograph of John B. Kisiel, M.D., of Mayo Clinic

John B. Kisiel, M.D.

A team of Mayo Clinic researchers has succeeded in identifying the source of cancer in patients' gastrointestinal tracts by analyzing DNA markers from tumors.

The results open the possibility that doctors could one day screen for cancer anywhere in the body with a noninvasive blood test or stool sample.

If proved practical and feasible, such screening tests could mean greater convenience for patients and saved lives through earlier diagnosis of cancer, especially rare and often fatal diseases such as pancreatic cancer and lung cancer.

"What's exciting about our discovery is that it allows us to stop thinking about screening organs and start thinking about screening people," said John B. Kisiel, M.D., a gastroenterologist at Mayo Clinic in Rochester, Minnesota. "As far as we are aware, this is the first series of experiments that has ever shown this concept."

Dr. Kisiel and his colleagues studied cancer-free patients and patients with cancers of the colon or pancreas. By collecting and identifying methylated DNA in a blood test, they were able to identify the presence and origin of the cancerous cells with about 80 percent accuracy.

"We think, based on the data we have, that a blood test could work in the future," Dr. Kisiel said.

Researchers double-checked their results by examining methylated DNA in tissue samples, identifying the origin of tumors with greater than 90 percent accuracy.

"Our work in tissue shows that we have fairly high precision," Dr. Kisiel said, "but you can't do a screening test in tissue, because you can't biopsy all these tissues at once as part of a screening test. That would not be practical."

The organ-by-organ search for cancer is precisely what Dr. Kisiel and colleagues hope to make unnecessary.

While biopsies in common malignancies such as breast cancer and prostate cancer have saved lives, screening for less common cancers is difficult because of the high risk of false-positive diagnoses, which can lead to unnecessary worrying and testing, Dr. Kisiel said.

As a result, Dr. Kisiel said, "a cancer like pancreatic cancer, although it's almost uniformly lethal, is not screened for at all in the general population, mainly because it's rare."

Finding and correctly identifying distinctive methylated DNA from the cancers in a blood or stool sample may change all that.

"DNA methylation may be a way to fingerprint not only the tissues themselves, but also the different types of cancer that might arise in those tissues," Dr. Kisiel said. "We hope that in the future patients might be able to submit a blood specimen and then we can analyze that blood specimen for the presence and absence of cancer markers. And if they are present, we hope to be able to determine the anatomic location of the tumor, or the organ from which it originates."

Dr. Kisiel's research applied specifically to the gastrointestinal tract. "We've not yet tested this concept in cancers throughout the entire body, but that is the next step," he said.

Comprehensive cancer screening by blood or stool sample won't be ready anytime soon, and patients should work with their doctors on appropriate cancer screening tests currently available.