TAG-CLL, a Novel Tagmentation-Based Approach to Somatic Hypermutation Testing of IGHV Reveals the Weak Points of Both Sanger and Next-Generation Sequencing Methods

Somatic hypermutation (SHM) status of IGHV gene, despite being a mature diagnostic biomarker in chronic lymphocytic leukemia (CLL), poses serious methodological problems for molecular laboratories. They may choose between inefficient Sanger sequencing protocols and expensive, recently developed next-generation sequencing–based methods. The performance of both types of methods seemed incomparable, and concerted validation of different protocols between laboratories was inconsiderable. Here, a new tagmentation-based approach to sequencing of IGHV locus is presented, which is agnostic to the amplification protocol used and enables direct comparison of the amplicons and libraries dedicated to different platforms (Sanger, IonTorrent, and Illumina).