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
Emanuela CarlottiJohn G Gribben

Abstract

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...Continue Reading

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Mar 10, 2016·Cancer Metastasis Reviews·Csaba Bödör, Lilla Reiniger
Nov 28, 2016·Hematology/oncology Clinics of North America·Mary Ann AndersonJohn F Seymour
Apr 19, 2018·Blood·Ralf Küppers, Freda K Stevenson
May 3, 2016·Current Opinion in Hematology·Jessica OkosunJude Fitzgibbon
Sep 2, 2016·Journal of Translational Medicine·Raffaele FrazziAlfredo Cesario
Oct 28, 2017·British Journal of Haematology·Matthew L Chase, Philippe Armand
Aug 15, 2018·Nature Immunology·Pierre MilpiedBertrand Nadel

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Datasets Mentioned

BETA
PRJEB9334

Methods Mentioned

BETA
biopsies
FACS
PCR
biopsy
PCRs
454 sequencing
454 deep sequencing
flow cytometry
flow-cytometry

Software Mentioned

IgTree
DIVA
FlowJo
ClustelW2

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