Gene mutation linked to deadly lymphoma

U. ROCHESTER (US) — The discovery of a gene mutation that drives a form of lymphoma that’s often difficult to treat suggests a new route for therapy.

“This opens the door for targeted therapy that may not cause the type of general toxicity we usually see with chemotherapy,” says Richard Fisher, a co-author on the study and a cancer researcher at the University of Rochester. Details are reported in the journal Nature.

An international consortium of scientists led by the National Cancer Institute used advanced gene sequencing techniques to uncover the MYD88 mutations in the least curable form of lymphoma, known as ABC subtype (activated B cell).

Remarkably, MYD88 mutations were observed in 29 percent of the biopsy samples involved in the study, while the mutation was rare or absent in other subtypes of lymphoma. This established MYD88 as among the most frequently altered gene in this malignancy, according to the study.

ABC lymphoma is a common type of diffuse large B cell lymphoma. The ability of ABC malignant cells to survive, despite treatment with chemotherapy and a newer drug, Rituximab, results in less than a 40 percent cure rate for this particular subtype.

Scientists used high-throughput RNA sequencing (a process of obtaining the order of molecules to better understand the genetic code) to uncover the MYD88 mutations in 382 biopsy samples and 35 lymphoma cell lines. They also identified the MYD88 signaling pathways integral to the development of ABC lymphoma, and learned that MYD88 coordinates a signaling “tower” consisting of various members of other important families of genes.

The study demonstrated what is required at the cellular level to maintain the viability of ABC cancer cells. By identifying the location of the mutation that is apparently unique to ABC, researchers believe they also located an enticing target for treatment, and perhaps a better way to genetically identify which patients might respond to a different combination of therapies.

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