Analysis of Ig/TCR repertoires by High-Throughput RNA Sequencing reveals a continuous dynamic of positive clonal selection in follicular lymphoma

High throughput RNA-sequencing was used to address simultaneously the BCR and TCR repertoires of lymphoma cells and their lymphoid microenvironment in follicular lymphoma. These data confirm the existence of a high degree of intra-clonal heterogeneity in this pathology, resulting from ongoing somatic hyper-mutation and class switch recombination. The evaluation of the Simpson ecological-diversity index also demonstrate that the contribution of the cancerous cells increases during the course of the disease to the detriment of the reactive compartment, a phenomenon accompanied by a concomitant decrease of the diversity of the tumoral population. Clonal evolution in FL thus contrasts with many tumors, where clonal heterogeneity steadily increases over time and participates to treatment evasion. In this pathology, the selection of lymphoma sub-clones with proliferative advantages progressively outweighs clonal diversification, ultimately leading in extreme cases to transformation to high-grade lymphoma resulting from the rapid emergence of homogeneous sub-populations.