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MPLN expands their oncology offering in CLL/SLL with IgVH Somatic Hypermutation by NGS


MPLN expands their oncology offering in CLL/SLL with IgVH Somatic Hypermutation by NGS
Posted on October 19, 2016 by Jonathan Mulkey

CLL/SLL is the most common leukemia diagnosed among adults in Western countries and is associated with heterogeneous clinical outcomes.  IgVH somatic hypermutation (SHM) status is a primary component of the CLL International Prognostic Index (CLL-IPI) working group formulation for disease risk stratification. Un-mutated IgVH has been established as a strong and independent predictor of adverse clinical prognosis and reduced overall survival.

Using a next generation sequencing-based approach to IgVH SHM detection, the MPLN methodology utilizes patient DNA as a sample starting material, eliminating many of the challenges related to RNA-based testing.  Laboratory workflow is streamlined and automated to result in non-subjective data output that includes percentage homology of clonal reads to germline IGH reference sequence, VDJ gene utilization, and frequencies of IGH gene sequences.

Traditionally, IgVH SHM has been evaluated by rt-PCR followed by Sanger Sequencing using patient sample RNA. However, RNA lability places a significant burden on the submitting physician to minimize specimen transit time. The Sanger Sequencing approach is also time and labor intensive and may show limited sensitivity in detection of IgVH SHM for low abundance clones. Flow cytometric analysis of ZAP-70 expression has therefore been widely utilized as a surrogate for IgVH SHM status, however standardization for this marker is known to be poor due to the subjective nature of its interpretation. Significant discordance between ZAP-70 expression patterns and IgVH SHM results may also be seen and has been attributed in some studies to pre-analytic sample processing factors.

Read more about IgVH Somatic Hypermutation testing

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