Next-Generation Sequencing Technique Diagnoses Recurrent Hodgkin’s Lymphoma

A next-generation sequencing-based approach can identify and quantify populations of B cells and detect tumor-specific DNA sequences in the blood of people with classical Hodgkin's lymphoma (CHL).

The test developed will allow physicians to better assess how patients have responded to initial treatment and to detect disease recurrence by simple blood draw instead of radiographic imaging studies.

Scientists at The University of Texas MD Anderson Cancer Center (Houston, TX, USA) obtained both primary tissue and blood samples from 17 CHL cases, taken either at the time of diagnosis or at recurrence were selected for evaluation. DNA and RNA were extracted from frozen primary tumor biopsy samples and analyzed for clonality at the immunoglobulin heavy chain (IGH) and kappa chain (IGK) loci using the high-throughput sequencing technology LymphoSIGHT method (Sequenta, Inc.; South San Francisco, CA, USA).

Minimal residual disease (MRD) refers to cancer cells that may remain in the body of a person with lymphoid cancer after treatment. These cells are present at levels undetectable by traditional microscopic examination, also called morphologic examination, of blood, bone marrow or a lymph node biopsy. Sensitive molecular technologies, such as the next-generation sequencing utilized by the clonoSEQ MRD test (Adaptive Biotechnologies, Seattle WA, USA), are needed for reliable detection of very low levels of MRD.

With its ability to detect cancer cells at a level as low as one per one million white blood cells, the clonoSEQ MRD test is one to two orders of magnitude more sensitive than the other methods of MRD detection. Seventeen CHL cases were tested and lymphoma-specific sequences were identified in 12 of the primary tumor biopsies. Lymphoma-specific sequences were identified in the serum from eight of 11 cases. The lymphoma-specific sequence was more frequently detected in serum than in peripheral blood mononuclear cells (PBMC), suggesting that the circulating lymphoma cells may lyse easily in the blood, or, more likely, DNA may be released directly from the tumor into the circulation. ClonoSEQ is a recent addition to the Adaptive portfolio thanks to its acquisition of Sequenta in January. The combined company aims to create novel immunosequencing products to diagnose, treat, and monitor patients with cancer, autoimmune disorders and infectious diseases.

Tom Willis, PhD, Senior Vice President and General Manager, Diagnostics Products, Adaptive Biotechnologies, said, “The immunosequencing technology that was used in this study allows for ultrasensitive detection of lymphoma-specific DNA signatures. This technology is at the heart of our clonoSEQ process, which has so far been validated for the detection and quantification of minimal residual disease in myeloma and several types of leukemia and non-Hodgkin's lymphoma. This study shows that our technology also has the potential to impact the clinical care of patients with Hodgkin's lymphoma.” The study was published on March 29, 2015, in the British Journal of Haematology.

Related Links:
The University of Texas MD Anderson Cancer Center
Sequenta Inc.
Adaptive Biotechnologies