Genetic Screen Predicts T-Cell Lymphoma Aggression

Sequencing of a single gene can spot patients with a dangerous form of mycosis fungoides better than other prognostic tests.  

Kerry Grens
Kerry Grens
May 9, 2018

Painting of a woman with mycosis fungoidesST. BARTHOLOMEW'S HOSPITAL ARCHIVES & MUSEUM, WELLCOME COLLECTIONA form of T-cell lymphoma called mycosis fungoides won’t kill the vast majority of patients if found early enough. But for about 20 percent of people with the cancer, the disease shrugs off treatments, progresses rapidly, and threatens patients’ lives. Reporting today (May 9) in Science Translational Medicine, researchers have been able to distinguish between the two types of mycosis fungoides (MF) by sequencing a single gene called TCRB, which encodes a receptor on T cells.

“While more work needs to be done, we think this approach has the potential to prospectively identify a subgroup of patients who are destined to develop aggressive, life-threatening disease,” study coauthor Thomas Kupper of Brigham and Women’s Hospital in Boston says in a press release, “and treat them in a more aggressive fashion with the intent to better manage, and ideally cure, their cancer.” 

Although MF is the most common type of cutaneous T-cell lymphoma (blood cancer that results in skin lesions), MF itself isn’t that common, affecting one of out every 100,000–350,000 people, according to the National Institutes of Health. Over the course of 15 years, Kupper and his colleagues collected samples from the skin lesions of hundreds of patients and sequenced TCRB in each to see if the team could spot a pattern of cancer progression.

It turned out that the tumor-clone frequency—that is, the proportion of T cells that bear the genetic marks of malignant cells—could predict with high accuracy which patients would go on to develop aggressive MF. Samples with tumor-cell clones representing more than 25 percent of the T cells were tied to a much greater risk for progression.

The method worked better than the usual technique of histologically examining the skin. “Under the microscope, benign T cell and MF T cells are hard to distinguish,” says Kupper. “However, every T cell has a unique DNA sequence of its T cell receptor. . . . High throughput DNA sequencing and calculations of [tumor-clone frequency] allow us to make predictions that would never before have been possible.”