Researchers say hybrid capture sequencing is an accurate and sensitive method for identifying actionable gene mutations in lymphoid malignancies.
This method revealed potentially actionable mutations in 91% of patients studied, who had diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), or chronic lymphocytic leukemia (CLL).
The researchers therefore believe hybrid capture sequencing will bring the benefits of precision diagnosis and individualized therapy to patients with lymphoid malignancies.
“To realize the benefits of the most recent progress in cancer genomics, clinical implementation of precision medicine approaches is needed in the form of novel biomarker assays,” said study author Christian Steidl, MD, of the University of British Columbia in Vancouver, Canada.
“Fully implemented targeted sequencing-based assays in routine diagnostic pathology laboratories are currently lacking in lymphoid cancer care. Our findings demonstrate the feasibility and outline the clinical utility of integrating a lymphoma-specific pipeline into personalized cancer care.”
Dr Steidl and his colleagues reported these findings in The Journal of Molecular Diagnostics.
The researchers first compared capture hybridization and amplicon sequencing using samples from 8 patients with lymphoma. Fresh-frozen and formalin-fixed, paraffin-embedded tumor samples were sequenced using a panel of 20 lymphoma-specific genes.
The team found that capture hybridization provided “deep, more uniform coverage” and yielded “higher sensitivity for variant calling” than amplicon sequencing.
The researchers then developed a targeted sequencing pipeline using a 32-gene panel. The panel was developed with input from a group of 6 specialists who kept updating it based on the latest available information.
“This allows for continuous integration of additional gene features as our knowledge base improves,” Dr Steidl noted.
He and his colleagues then applied the hybrid capture sequencing assay and 32-gene panel to tissues from 219 patients—114 with FL, 76 with DLBCL, and 29 with CLL—who were treated in British Columbia between 2013 and 2016.
Results revealed at least one actionable mutation in 91% of the tumors. And the assay uncovered subtype-specific mutational profiles that were highly similar to published mutational profiles for FL, DLBCL, and CLL.
Furthermore, the assay had 93% concordance with whole-genome sequencing.
“Our developed assay harnesses the power of modern sequencing for clinical diagnostics purposes and potentially better deployment of novel treatments in lymphoid cancers,” Dr Steidl said. “We believe our study will help establish evidence-based approaches to decision making in lymphoid cancer care.”
“The next steps are to implement sequencing-based biomarker assays, such as reported in our study, in accredited pathology laboratories. Toward the goal of biomarker-driven clinical decision making, testing of potentially predictive biomarker assays is needed alongside clinical trials investigating novel cancer therapeutics.”