Genome Sequencing of Classical Hodgkin Lymphoma Cells Opens Door to Personalized Treatment

Researchers have sequenced the genomes of 10 patients with classical Hodgkin lymphoma (cHL), cataloging the mutations in the Reed-Sternberg (RS) cells that characterize cHL. This was reported in the February 12, 2015 issue of Blood, the journal from the American Society of Hematology (ASH).

This discovery that shows which patients' proteins are altered didn't come easy. Because of the difficulty of parsing the RS cells from the neoplastic DNA without causing background contamination, this process has been challenging. Senior study author Ethel Cesarman, MD, professor of pathology and laboratory medicine at Weill Cornell Medical College, and colleagues overcame some of the challenges by using flow-sorted RS and intratumor T-cells, and optimized low-input exome sequencing of 10 patient samples to reveal alterations in genes involved in antigen presentation, chromosome integrity, transcriptional regulation, and ubiquitination.

Beta2-microglobulin (B2M) is the most frequently mutated gene in cHL, and is characterized by a nodular sclerosis subtype, meaning that the involved lymph nodes contain RS cells with normal white blood cells. This subtype accounts for 60% to 80% of of all HL cases. B2M is also characterized by a younger age of diagnosis, but a greater chance of overall survival and progression-free survival, with up to 80% cure rates.

Approximately 30% of patients experience relapse in advanced-stage cHL, and up to 10% of newly diagnosed patients may not experience remission, so these new findings may help determine which group of patients--with different mutations--could benefit from more aggressive therapy.

Because of these new findings, researchers may be able to develop drugs that target these specific alterations to compensate for these gene mutations. Though this discovery may lay the groundwork for personalized treatment based on specific cells in cHL, a larger sample size in future research will be necessary to further elucidate how successful it will be for this multifaceted disease.

“Our methodology provides an opportunity for further prospective comprehensive genomic exploration of the less common subtypes of cHL and of treatment-resistant and recurrent disease,” the researchers conclude.