Immunoglobulin Heavy-Chain (IGH) Hypermutation (IGH V Region) Sequencing (LAB9774)

Somatic hypermutation (SHM) status in the IGHV gene offers prognostic information for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). A mutation difference of ≥ 2% from the germline IGHV gene is defined as hypermutation, while <2% difference is considered as no somatic hypermutation. Patients with unmutated IGHV have a poor prognosis and significantly decreased survival compared with mutated IGHV, regardless of the disease stage.

IGHV hypermutation testing is performed at the Molecular Diagnostic Laboratory at Barnes-Jewish Hospital, Institute of Health, with peripheral blood and bone marrow as the required specimens. The laboratory-developed test leverages next-generation sequencing approaches to identify the predominant clonal rearrangement and provide nucleotide-level resolution, potentially aiding in monitoring disease progression over time.

• IGHV hypermutation testing is not intended to confirm or exclude a diagnosis of CLL, but serves as an adjunct to establish prognosis.

• Assessment of the SHM status of the IGHV gene is recommended for all patients with CLL/SLL before therapy initiation, as advised by the WHO and NCCN.
• Testing may add relevant diagnostic information in the assessment of measurable residual disease.

1. Gupta SK, Viswanatha DS, Patel KP. Evaluation of Somatic Hypermutation Status in Chronic Lymphocytic Leukemia (CLL) in the Era of Next Generation Sequencing. Front Cell Dev Biol. 2020 May 19;8:357. doi: 10.3389/fcell.2020.00357. PMID: 32509784; PMCID: PMC7248390.