Are You Testing for DTX1 in Your Lymphoma Trial? What About FAT2 or FAT4? The CGI Team has Designed Focus::Lymphoma NGS to Interrogate the Genes You Need.

Written by: JamieThalmann

Published on:
April 12th, 2016

A growing body of research is describing the benefits of broad, hybrid capture NGS as a method of comprehensive and efficient genomic profiling to guide precision medicine. With the rise of multi-arm or basket trials, and the limitations of technologies such as IHC this design is well on the way to becoming the first line approach.

More than 300 driver mutations have been associated with DLBCL, the most aggressive subtype of B-cell lymphoma.  Drawing on more than a decade of clinical expertise in B-cell malignancies, CGI has been able to capture the complexity of the genomic landscape in DLBCL and other non-Hodgkin’s lymphomas. CLIA certification now allows our newest NGS panel – Focus::Lymphoma to move beyond research into full clinical availability.

Focus::Lymphoma covers 220 genes with a known mutation profile in DLBCL, FL, MCL, and CLL/SLL, including those recurrently mutated with a frequency of greater than 5%. Additionally, we have the capacity to report single copy genomic changes across the genome. The panel architecture was targeted to include genes with prognostic implications as well as those associated with GBC and ABC subtypes, and MYC/BCL2 “double-hit” lymphomas.  For example, DTX1, a NOTCH1 pathway regulator, has been reported to be mutated in ~14% of DLBCL patients displaying reduced 5 year OS regardless of GBC or ABC status.

We’ve prioritized inclusion of targets associated with both approved and clinically late-stage therapies to provide the insight necessary to evaluate future combination regimes. Uniquely, the panel represents enriched pathways such as BCR signaling, PI3K, WNT signaling, and focal adhesion, and those associated with resistance to inhibitors of these pathways.

Focus::Lymphoma was a featured CGI platform at ASH 2015. Look for the upcoming publication of our article: Characterization of a variant of t(14;18) negative nodal diffuse follicular lymphoma with CD23 expression, 1p36/TNFRSF14 abnormalities, and STAT6 mutations in Modern Pathology, wherein the NGS panel has been used to characterize both the mutation and copy number profile of this FL variant.

Our Lymphoma panel is already being integrated into several industry-leading B-cell malignancy trials.  Whether you are interested in retrospectively profiling previous clinical trial cohorts – or incorporating these data into an exploratory endpoint of an upcoming trial, we have designed Focus::Lymphoma with reproducibility and therapeutic impact foremost in mind.