| Added by | Nathalie Bonnefoy |
|---|---|
| Group name | EquipeNB |
| Item Type | Journal Article |
| Title | Comprehensive characterization of immunoglobulin gene rearrangements in patients with chronic lymphocytic leukaemia |
| Creator | René et al. |
| Author | Céline René |
| Author | Nathalie Prat |
| Author | Audrey Thuizat |
| Author | Mélanie Broctawik |
| Author | Odile Avinens |
| Author | Jean-François Eliaou |
| Abstract | Previous studies have suggested a geographical pattern of immunoglobulin rearrangement in chronic lymphocytic leukaemia (CLL), which could be as a result of a genetic background or an environmental antigen. However, the characteristics of Ig rearrangements in the population from the South of France have not yet been established. Here, we studied CLL B-cell repertoire and mutational pattern in a Southern French cohort of patients using an in-house protocol for whole sequencing of the rearranged immunoglobulin heavy-chain genes. Described biased usage of variable, diversity and joining genes between the mutated and unmutated groups was found in our population. However, variable gene frequencies are more in accordance with those observed in the Mediterranean patients. We found that the third complementary-determining region (CDR) length was higher in unmutated sequences, because of bias in the diversity and joining genes usage and not due to the N diversity. Mutations found in CLL followed the features of canonical somatic hypermutation mechanism: preference of targeting for activation-induced cytidine deaminase and polymerase motifs, base change bias for transitions and more replacement mutations occurring in CDRs than in framework regions. Surprisingly, localization of activation-induced cytidine deaminase motifs onto the variable gene showed a preference for framework regions. The study of the characteristics at the age of diagnosis showed no difference in clinical outcome, but suggested a tendency of increased replacement and transition-over-transversion mutations and a longer third CDR length in older patients. |
| Publication | Journal of Cellular and Molecular Medicine |
| Volume | 18 |
| Issue | 6 |
| Pages | 979-990 |
| Date | Jun 2014 |
| Journal Abbr | J. Cell. Mol. Med. |
| Language | eng |
| DOI | 10.1111/jcmm.12215 |
| ISSN | 1582-4934 |
| Library Catalog | PubMed |
| Extra | PMID: 24725733 PMCID: PMC4508139 |
| Tags | Aged, ageing, AID, CDR3, CLL, DNA, Neoplasm, Female, first-last-corresponding, Gene Rearrangement, Genes, Immunoglobulin, Humans, immunoglobulin, Immunoglobulin Heavy Chains, Immunoglobulin J-Chains, Immunoglobulin Variable Region, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Mutation, original, Prognosis, Real-Time Polymerase Chain Reaction, somatic hypermutation |
| Date Added | 2019/05/28 - 21:32:34 |
| Date Modified | 2019/05/28 - 21:32:58 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
