S(mu) mutation patterns suggest different progression pathways in follicular lymphoma: early direct or late from FL progenitor cells.
Follicular lymphoma (FL) is a B-cell malignancy characterized by the t(14;18) translocation. Although sensitive to treatment, the disease remains incurable and the reason why tumor cells invariably evade treatment, leading to clinical relapse, is still unknown. Here, we tracked the clonal history of tumor cells by studying mutations introduced by activation-induced cytidine deaminase on the switch mu region of the der(14)t(14;18) during the early phase of the class-switch recombination (CSR) process. We observed frequent intraclonal variations, suggesting that CSR often remains active after the acquisition of the fully transformed phenotype. However, mutations only rarely accumulated over time, but instead showed complex evolutionary scenarios and 2 different progression pathways. The first pathway was a direct and rapid evolution from the dominant clone. The second was indirect, arising from earlier subclones usually after years of remission. A better understanding of these mechanisms might influence the future choice of treatment strategies.
Inserm U918, Groupe d'étude des Proliférations Lymphoïdes, Institut Federatif de Recherches Multidisciplinaires sur les Peptides 23 (IFRMP23), France. phirum@rouen.fnclcc.fr
Philippe
P
Ruminy
Fabrice
F
Jardin
Jean-Michel
JM
Picquenot
Françoise
F
Parmentier
Nathalie
N
Contentin
Gérard
G
Buchonnet
Sandrine
S
Tison
Vinciane
V
Rainville
Hervé
H
Tilly
Christian
C
Bastard
D001483:Base Sequence; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D003564:Cytidine Deaminase / Q000378:metabolism; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D017578:Immunoglobulin Class Switching; D007134:Immunoglobulin Switch Region; D008224:Lymphoma, Follicular / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D013997:Time Factors; D014178:Translocation, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D017931:DNA Primers; D004273:DNA, Neoplasm; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase