Cargando…
Comprehensive characterization of immunoglobulin gene rearrangements in patients with chronic lymphocytic leukaemia
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...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508139/ https://www.ncbi.nlm.nih.gov/pubmed/24725733 http://dx.doi.org/10.1111/jcmm.12215 |
_version_ | 1782381898758094848 |
---|---|
author | René, Céline Prat, Nathalie Thuizat, Audrey Broctawik, Mélanie Avinens, Odile Eliaou, Jean-François |
author_facet | René, Céline Prat, Nathalie Thuizat, Audrey Broctawik, Mélanie Avinens, Odile Eliaou, Jean-François |
author_sort | René, Céline |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4508139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45081392015-07-22 Comprehensive characterization of immunoglobulin gene rearrangements in patients with chronic lymphocytic leukaemia René, Céline Prat, Nathalie Thuizat, Audrey Broctawik, Mélanie Avinens, Odile Eliaou, Jean-François J Cell Mol Med Original Articles 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. John Wiley & Sons, Ltd 2014-06 2014-04-11 /pmc/articles/PMC4508139/ /pubmed/24725733 http://dx.doi.org/10.1111/jcmm.12215 Text en © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles René, Céline Prat, Nathalie Thuizat, Audrey Broctawik, Mélanie Avinens, Odile Eliaou, Jean-François Comprehensive characterization of immunoglobulin gene rearrangements in patients with chronic lymphocytic leukaemia |
title | Comprehensive characterization of immunoglobulin gene rearrangements in patients with chronic lymphocytic leukaemia |
title_full | Comprehensive characterization of immunoglobulin gene rearrangements in patients with chronic lymphocytic leukaemia |
title_fullStr | Comprehensive characterization of immunoglobulin gene rearrangements in patients with chronic lymphocytic leukaemia |
title_full_unstemmed | Comprehensive characterization of immunoglobulin gene rearrangements in patients with chronic lymphocytic leukaemia |
title_short | Comprehensive characterization of immunoglobulin gene rearrangements in patients with chronic lymphocytic leukaemia |
title_sort | comprehensive characterization of immunoglobulin gene rearrangements in patients with chronic lymphocytic leukaemia |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508139/ https://www.ncbi.nlm.nih.gov/pubmed/24725733 http://dx.doi.org/10.1111/jcmm.12215 |
work_keys_str_mv | AT reneceline comprehensivecharacterizationofimmunoglobulingenerearrangementsinpatientswithchroniclymphocyticleukaemia AT pratnathalie comprehensivecharacterizationofimmunoglobulingenerearrangementsinpatientswithchroniclymphocyticleukaemia AT thuizataudrey comprehensivecharacterizationofimmunoglobulingenerearrangementsinpatientswithchroniclymphocyticleukaemia AT broctawikmelanie comprehensivecharacterizationofimmunoglobulingenerearrangementsinpatientswithchroniclymphocyticleukaemia AT avinensodile comprehensivecharacterizationofimmunoglobulingenerearrangementsinpatientswithchroniclymphocyticleukaemia AT eliaoujeanfrancois comprehensivecharacterizationofimmunoglobulingenerearrangementsinpatientswithchroniclymphocyticleukaemia |