Noninvasive sampling of diffuse large B-cell lymphoma (DLBCL) circulating tumor DNA enables early detection of focal and broad somatic copy number alterations, according to research that will be presented at the 2017 ASCO Annual Meeting (June 2-6, 2017; Chicago, IL).
Somatic copy number alterations are common and are clinically significant genomic events in DLBCL. Previous research has shown that MYC and BCL2 amplifications correlate with adverse events, whereas PD-L1 amplifications are associated with better response to immune checkpoint inhibitors in such disease. However, noninvasive detection of somatic copy number alterations from circulating tumor DNA remains a challenge.
A team of multinational hematologists successfully utilized a targeted high-throughput sequencing platform to develop a method of profiling both focal and broad somatic copy number alterations from plasma. Researchers profiled plasma samples from a cohort of 75 patients with DLBCL prior to treatment, as well as 48 healthy control patients. After focal somatic copy number alterations were evaluated at significantly high depths to allow for detection of lesions at 1% of circulating tumor DNA fraction, thresholds were adjusted to allow a false positive rate of 1%.
Sequencing reads outside of the targeted regions were pooled separately and analyzed to assess arm and chromosome level somatic copy number alterations.
Researchers detected somatic copy number alterations in multiple clinically relevant genes, including amplifications in MYC (8.0%), BCL2 (24.0%), and BCL6 (14.7%), as well as deletions in TP53 (13.3%) and CDKN2A (9.3%).
Additionally, researchers observed 26.7% of patients demonstrated amplified PD-L1 and PD-L2. PD-L1 amplifications were reported to be more common in patients with relapsed DLBCL than in those with treatment-naïve disease (43.5% vs 19.2%, respectively; P = .02).
Authors of the study concluded that noninvasive sampling of DLBCL circulating tumor DNA can successfully detect focal and broad somatic copy number alterations, particularly amplifications of MYC, BCL2, and PD-L1. “The ability to noninvasively profile copy number altered regions allows for biopsy-free discovery of clinically significant structural alterations in lymphoma patients,” they wrote.
Further tissue profiling data is currently under review.—Zachary Bessette
