Evolutionary dynamics and driver mutations underlying histological transformation and treatment resistance in follicular lymphoma

Lymphoid cancers arise from lymphocytes, a subset of white blood cells, and represent the fifth most common cause of cancer. Follicular lymphoma (FL) is a common subtype of lymphoid cancers. For ten percent of FL patients, the disease either does not respond to primary therapy or progresses early after treatment. These patients have poor outcomes and often require aggressive therapeutic interventions.

With regards to its origin, FL demonstrates how cancers arise through the successive acquisition of changes in their genomes. In his research, Dr. Kridel’s group has identified highly recurrent mutations in certain genes which delineate disease-initiating mechanisms. Yet, the biological underpinnings of treatment resistance and transformation in FL are only partially understood.

Dr. Kridel hypothesizes that both resistance to therapy and transformation can be explained by genetic alterations that are either present at diagnosis and get selected for during therapy, or that arise during the course of the disease. Thus, Dr. Kridel’s team will apply high-throughput genome sequencing technology to paired FL and progressed/transformed lymphoma samples. Dr. Kridel will leverage the availability of tumour specimens from the tissue repository of the Centre for Lymphoid Cancer at the BC Cancer Agency and collaborate with the Computational Biology group of Dr. Sohrab Shah, who has developed cutting-edge tools to examine genome-wide mutational changes.

The goal is to improve patient outcomes by understanding the genetic mechanisms that drive treatment resistance, early progression and transformation in FL.