Use of IGHJ and IGHD gene mutations in analysis of immunoglobulin sequences for the prognosis of chronic lymphocytic leukemia

• Published in: Leukemia research Vol. 31; no. 9; pp. 1247 - 1252
• Main Authors: Lee, Cindy E.H, Jackson, Katherine J.L, Sewell, William A, Collins, Andrew M
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2007
• Subjects: Chronic lymphocytic leukemia; Computational Biology; Databases, Nucleic Acid; Gene Frequency; Hematology, Oncology and Palliative Medicine; Humans; IGHJ; Immunoglobulin; Immunoglobulin delta-Chains - genetics; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Joining Region - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Mutation - genetics; Prognosis; Repertoire development; Somatic mutation; Somatic mutation; Chronic lymphocytic leukemia; IGHJ; Immunoglobulin; Repertoire development
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2006.10.013

Abstract The level of somatic point mutation in immunoglobulin genes is an important prognostic indicator for patients with chronic lymphocytic leukemia (CLL). Mutation analysis presently focuses solely upon the heavy chain IGHV gene, however mutation is a stochastic process that also targets IGHD and IGHJ genes. Here, we evaluate the completeness and reliability of the reported IGHJ gene repertoire, and demonstrate the likely consequences of the inclusion of IGHD and IGHJ mutations in CLL analysis, using a dataset of 607 sequences. Inclusion of these mutations would lead to the re-classification of many sequences, which should significantly improve the prognostic value of mutation analysis.