Identifying lymphoma antigen receptor sequences by immune repertoire profiling (TUM2P.915)

Abstract

Abstract Neoplastic T and B cells rapidly expand, leading to T and B-cell receptor (TCR and BCR) repertoires dominated by one rearrangement. However clones reacting to an antigen also expand. Differentiating high-frequency reactive clones from lymphomas is important for both diagnosing and monitoring lymphomas. To document the diverse repertoire of TRB and IGH CDR3 chains, we developed a method to deeply sequence the CDR3 rearrangements using high-throughput sequencing (HTS). This technology provides a potential opportunity to identify and monitor neoplastic clones during the course of therapy. To demonstrate the potential of HTS of T and B-cell receptors to contribute to diagnosing and monitoring neoplasia in mature lymphomas; we amplify the TCR repertoire of 98 and the BCR repertoire of 60 index samples to identify high-frequency TRB or IGH rearrangements. Concurrently, we sequence the TRB and IGH repertoire in control blood, bone marrow, and reactive lymph tissue. Clones are classified as neoplastic if occurring at a proportion greater than 7 standard deviations above the mean frequency of the most abundant rearranged TRB or IGH in control samples. Using these criteria, Eighty-four percent of index samples have a tractable rearrangement. We find that for most disease diagnoses, high-throughput sequencing identifies a tractable clone and T-cell and B-cell receptor repertoire analysis may be useful for clinical laboratory evaluation of patients with T and B-cell neoplasms.