Authors: Jeran Stratford, Jennifer Sims, Victor Weigman and Patrick Hurban
High-throughput sequencing of immune repertoire is increasingly used for clinical diagnosis, monitoring of residual disease, and development of cancer immunotherapies. The somatic hypermutations load in the rearranged immunoglobulin heavy-chain variable region gene (IGHV) is a powerful prognostic biomarkers in CLL. CLL arising from unmutated IGHV cells (≥98% identity to closest germline rearrangement) are more aggressive and associate with poor prognosis, while CLL with mutated IGHV (<98% identity) have favorable outcomes and a higher rate of durable remissions after treatment with chemoimmunotherapy combinations. Historically, IGHV mutation status has been performed using Sanger sequencing looking at a single dominant clone. However, next-generation sequencing can reveal the sample's IGHV diversity.
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