New assay may allow screening for 'actionable' gene mutations in routinely acquired archival biopsies.

‘The new assay targets a select set of genes or regions with known associations with lymphoid cancer, allowing for more rapid detection of a variety of mutations.’

Lymphoid cancers include diffuse large B-cell lymphomas (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL), which were the focus of the present study. In recent years, several sequencing-based assays have been developed, but their clinical applicability and utility for patients with specific mutations still needs to be shown. Actionable gene mutations are defined by having a reported correlation with treatment outcome, a molecular association with a particular targeted therapy, or increasing pathologic-diagnostic accuracy. Currently, most genetic mutations associated with lymphoid cancers have been identified. 




"This study is remarkably comprehensive, which will help any molecular laboratory design and implement their own next-generation sequencing lymphoma panel using this work as a template," commented Robert S. Ohgami, MD, PhD, Assistant Professor of Pathology at the Stanford University Medical Center, in an accompanying editorial.
Unlike whole-genome sequencing, this assay targets a select set of genes or regions with known associations with lymphoid cancer, allowing for more rapid detection of a variety of mutations. According to this study, capture hybridization is a better method over amplicon-based sequencing, when using formalin-fixed, paraffin-embedded tissue.
Also, this assay is continuously modifiable due to its modular flexible design. The 32-gene next-generation sequencing panel described in the paper was developed with input from a group of six 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," added Dr. Steidl.
The investigators applied the assay to tissues from 219 patients with lymphoid cancers (114 FL, 76 DLBCL, and 29 CLL) who were treated in British Columbia, Canada, between 2013 and 2016. At least one actionable mutation was found in 91 percent of the tumors. The assay revealed cancer subtype-specific mutational profiles that were highly similar to published mutational profiles for all three types of lymphoid cancer. The assay was also found to have 93 percent concordance with whole-genome sequencing.
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