‘Liquid Biopsy’ Detects DLBCL Gene Copy Number Alterations

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Prognostic somatic copy number alterations in diffuse large B-cell lymphoma can be detected and monitored noninvasively using ctDNA from patient plasma.

CHICAGO-Prognostic somatic copy number alterations (SCNAs) in diffuse large B-cell lymphoma (DLBCL) can be detected and monitored noninvasively using circulating tumor DNA (ctDNA) from patient plasma, according to study results (abstract 7507) presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6.

“For the majority of DLBCL patients, copy number alterations are noninvasively detectable at diagnosis,” reported lead study author Michael C. Jin, MD, of the division of oncology at Stanford University School of Medicine in Stanford, California. “Noninvasive sampling of lymphoma ctDNA enables detection of both focal and broad SCNAs, including 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.”

ctDNA-detected amplifications in MYC and BCL2 were prognostic of worse survival, as were TP53 deletions, Jin added.

The authors analyzed pretreatment plasma samples from 168 patients with DLBCL using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq) and genome-wide allele fraction and copy number alteration analyses. Sensitivity and specificity were particularly high in patients with high tumor burden (ctDNA > 5%), Jin said. Additional analyses were conducted using plasma from patients diagnosed with Hodgkin lymphoma and primary mediastinal B-cell lymphoma (PMBCL).

Plasma ctDNA allele fractions (frequencies) increased with disease stage (P < .05).

The authors profiled pretreatment plasma samples from 75 patients diagnosed with DLBCL and from 48 healthy controls.

Genome-wide ctDNA sequencing detected PD-L1 amplification in DLBCL, PMBCL, and classical Hodgkin lymphoma cells, Jin reported. “We detected a high frequency of PD-L1 lesions in DLBCL, which may be relevant for patient selection in future checkpoint immunotherapy trials.”

BCL2, BCL6, and PD-L1 gene amplifications were significantly less common in germinal center B-cell–like (GCB) DLBCL than non-GCB molecular subtype DLBCL (P < .05). BCL2 amplifications were detected in 39% of non-GCB cells vs 17% of GCB cells, and BCL6 was found in 31% of non-GCB DLBCLs vs 15% of GCB DLBCLs. PD-L1 amplifications were seen in 39% and 25% of non-GCB and GCB disease, respectively.

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