High Throughput Sequencing Analysis of the Immunoglobulin Heavy Chain Gene from Flow-Sorted B Cell Sub-Populations Define the Dynamics of Follicular Lymphoma Clonal Evolution.
Understanding the dynamics of evolution of Follicular Lymphoma (FL) clones during disease progression is important for monitoring and targeting this tumor effectively. Genetic profiling of serial FL biopsies and examples of FL transmission following bone marrow transplant suggest that this disease m...
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0134833&type=printable |
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| author | Emanuela Carlotti David Wrench Guglielmo Rosignoli Jacek Marzec Ajanthah Sangaralingam Lena Hazanov Miri Michaeli Simon Hallam Tracy Chaplin Sameena Iqbal Maria Calaminici Bryan Young Ramit Mehr Peter Campbell Jude Fitzgibbon John G Gribben |
| author_facet | Emanuela Carlotti David Wrench Guglielmo Rosignoli Jacek Marzec Ajanthah Sangaralingam Lena Hazanov Miri Michaeli Simon Hallam Tracy Chaplin Sameena Iqbal Maria Calaminici Bryan Young Ramit Mehr Peter Campbell Jude Fitzgibbon John G Gribben |
| author_sort | Emanuela Carlotti |
| collection | DOAJ |
| description | Understanding the dynamics of evolution of Follicular Lymphoma (FL) clones during disease progression is important for monitoring and targeting this tumor effectively. Genetic profiling of serial FL biopsies and examples of FL transmission following bone marrow transplant suggest that this disease may evolve by divergent evolution from a common ancestor cell. However where this ancestor cell resides and how it evolves is still unclear. The analysis of the pattern of somatic hypermutation of the immunoglobulin gene (Ig) is traditionally used for tracking the physiological clonal evolution of B cells within the germinal center and allows to discriminate those cells that have just entered the germinal center and display features of ancestor cells from those B cells that keep re-circulating across different lymphoid organs. Here we investigated the pattern of somatic hypermutation of the heavy chain of the immunoglobulin gene (IgH-VH) in 4 flow-sorted B cells subpopulations belonging to different stages of differentiation, from sequential lymph node biopsies of cases displaying diverse patterns of evolution, using the GS-FLX Titanium sequencing platform. We observed an unexpectedly high level of clonality, with hundreds of distinct tumor subclones in the different subpopulations from the same sample, the majority detected at a frequency <10-2. By using a lineage trees analysis we observed in all our FL and t-FL cases that the oligoclonal FL population was trapped in a narrow intermediate stage of maturation that maintains the capacity to undergo SHM, but was unable to further differentiate. The presence of such a complex architecture highlights challenges currently encountered in finding a cure for this disease. |
| format | Article |
| id | doaj-art-69bd4bb7c9f7459aa46cb9de4b5b04a4 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-69bd4bb7c9f7459aa46cb9de4b5b04a42025-08-20T03:10:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013483310.1371/journal.pone.0134833High Throughput Sequencing Analysis of the Immunoglobulin Heavy Chain Gene from Flow-Sorted B Cell Sub-Populations Define the Dynamics of Follicular Lymphoma Clonal Evolution.Emanuela CarlottiDavid WrenchGuglielmo RosignoliJacek MarzecAjanthah SangaralingamLena HazanovMiri MichaeliSimon HallamTracy ChaplinSameena IqbalMaria CalaminiciBryan YoungRamit MehrPeter CampbellJude FitzgibbonJohn G GribbenUnderstanding the dynamics of evolution of Follicular Lymphoma (FL) clones during disease progression is important for monitoring and targeting this tumor effectively. Genetic profiling of serial FL biopsies and examples of FL transmission following bone marrow transplant suggest that this disease may evolve by divergent evolution from a common ancestor cell. However where this ancestor cell resides and how it evolves is still unclear. The analysis of the pattern of somatic hypermutation of the immunoglobulin gene (Ig) is traditionally used for tracking the physiological clonal evolution of B cells within the germinal center and allows to discriminate those cells that have just entered the germinal center and display features of ancestor cells from those B cells that keep re-circulating across different lymphoid organs. Here we investigated the pattern of somatic hypermutation of the heavy chain of the immunoglobulin gene (IgH-VH) in 4 flow-sorted B cells subpopulations belonging to different stages of differentiation, from sequential lymph node biopsies of cases displaying diverse patterns of evolution, using the GS-FLX Titanium sequencing platform. We observed an unexpectedly high level of clonality, with hundreds of distinct tumor subclones in the different subpopulations from the same sample, the majority detected at a frequency <10-2. By using a lineage trees analysis we observed in all our FL and t-FL cases that the oligoclonal FL population was trapped in a narrow intermediate stage of maturation that maintains the capacity to undergo SHM, but was unable to further differentiate. The presence of such a complex architecture highlights challenges currently encountered in finding a cure for this disease.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0134833&type=printable |
| spellingShingle | Emanuela Carlotti David Wrench Guglielmo Rosignoli Jacek Marzec Ajanthah Sangaralingam Lena Hazanov Miri Michaeli Simon Hallam Tracy Chaplin Sameena Iqbal Maria Calaminici Bryan Young Ramit Mehr Peter Campbell Jude Fitzgibbon John G Gribben High Throughput Sequencing Analysis of the Immunoglobulin Heavy Chain Gene from Flow-Sorted B Cell Sub-Populations Define the Dynamics of Follicular Lymphoma Clonal Evolution. PLoS ONE |
| title | High Throughput Sequencing Analysis of the Immunoglobulin Heavy Chain Gene from Flow-Sorted B Cell Sub-Populations Define the Dynamics of Follicular Lymphoma Clonal Evolution. |
| title_full | High Throughput Sequencing Analysis of the Immunoglobulin Heavy Chain Gene from Flow-Sorted B Cell Sub-Populations Define the Dynamics of Follicular Lymphoma Clonal Evolution. |
| title_fullStr | High Throughput Sequencing Analysis of the Immunoglobulin Heavy Chain Gene from Flow-Sorted B Cell Sub-Populations Define the Dynamics of Follicular Lymphoma Clonal Evolution. |
| title_full_unstemmed | High Throughput Sequencing Analysis of the Immunoglobulin Heavy Chain Gene from Flow-Sorted B Cell Sub-Populations Define the Dynamics of Follicular Lymphoma Clonal Evolution. |
| title_short | High Throughput Sequencing Analysis of the Immunoglobulin Heavy Chain Gene from Flow-Sorted B Cell Sub-Populations Define the Dynamics of Follicular Lymphoma Clonal Evolution. |
| title_sort | high throughput sequencing analysis of the immunoglobulin heavy chain gene from flow sorted b cell sub populations define the dynamics of follicular lymphoma clonal evolution |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0134833&type=printable |
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