Tumor DNA Analysis Could Be Useful in Assessing Disease Course

Marisa Wexler MS avatar

by Marisa Wexler MS |

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Analyzing small amounts of tumor DNA that end up in the bloodstream could be useful for assessing the course of Cushing’s syndrome in patients whose disease is caused by a hormone-producing tumor, a new report illustrates.

In the case of a 45-year-old man in France, DNA changes “were well correlated with the disease course,” the researchers wrote.

While such analyses are expensive, the team acknowledged, they said the data such testing generates may help in developing more personalized treatments for people with Cushing’s syndrome.

The report, “cfDNA in pancreatic neuroendocrine carcinoma management with Cushing’s syndrome,” was published in the journal Endocrine Oncology.

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In the study, researchers in Lyon, France, and their colleagues, described the case of a man diagnosed with metastatic pancreatic neuroendocrine carcinoma. A neuroendocrine carcinoma, or NEC, is a type of tumor that can produce and release hormones. In this case, the NEC had formed in the patient’s pancreas and then spread to his liver.

Upon physical examination, the patient was found to have Cushing’s syndrome, caused by abnormally high levels of the stress hormone cortisol, as a result of excessive levels of a signaling molecule called adrenocorticotropic hormone (ACTH).

Brain imaging scans showed no abnormalities in the pituitary gland, indicating the patient did not have Cushing’s disease — a specific form of Cushing’s syndrome caused by a tumor in that regulatory gland.

Over the course of nearly two years, the patient underwent five different types of chemotherapy and other cancer treatments.

Starting from the second line of treatment, the patient’s circulating-free DNA, called cfDNA, was monitored. cfDNA, as its name suggests, is DNA that has been released and is circulating freely in the bloodstream.

According to the researchers, such DNA is released when cells die or are damaged — and cancer cells are no exception. As such, analyzing cfDNA from a tumor can allow investigators to gain insights into its genetic architecture without having to perform an invasive biopsy.

­“To our knowledge, the present study is the first report of a pancreatic NEC case for which repeated cfDNA analyses were performed,” the researchers wrote.

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cfDNA analyses revealed mutations in two well-documented cancer-associated genes, KRAS and TP53.

When the patient underwent his third line of treatment — a chemotherapy regimen called FOLFIRINOX — the amount of cfDNA with these mutations decreased, the researchers noted. This decrease was accompanied by a reduction in ACTH levels, and an overall health improvement.

However, when cancer progressed, the man’s symptoms worsened, and the amount of abnormal cfDNA increased yet again.

“The molecular changes [in cfDNA] were well correlated with the Cushing’s syndrome course … and with the tumour burden changes assessed,” the researchers wrote.

“This illustrates that cfDNA could be a useful tool to better identify subgroups of NEC patients and propose more personalised treatments,” they wrote.

The team acknowledged that cfDNA analyses are expensive, and require a lot of expertise and specialized equipment to perform. Though they did note that “its costs are gradually coming down.”

“Further studies are warranted to formally validate cfDNA as a biomarker that can be incorporated into routine clinical care,” the researchers concluded, moreover suggesting that “cfDNA use could improve NEC management in several ways.”

While some of the treatments in this case led to temporary improvements in the patient’s condition, the man’s cancer ultimately progressed, and he died in early 2020, the researchers noted.