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repository.cam.ac.ukJan 2024

23-285. R1 Poulsom-EDITED UK English BRIEF REPORT

Makker, J; Wotherspoon, A; Tzioni, MM; Chen, Z; Guo, S
Product Used
NGS
Abstract
Follicular lymphoma (FL) develops through a stepwise acquisition of cooperative genetic changes with t(14;18)(q32;q21)/IGH::BCL2 occurring early at the pre-B stage of B-cell development. Patients with FL typically show an indolent clinical course, remitting and relapsing with the eventual development of resistance to treatments. Interestingly, the majority of transformed FL do not progress directly from FL but originate from their clonally related lymphoma precursor cells (CLP). To examine whether such divergent tumour evolution also underpins the relapses in patients with early-stage FL, we investigated by targeted nextgeneration sequencing 13 cases (stage I=9; stage II=4), who showed complete remission (mean: 5 years; range: 1-11.5 years) following local radiotherapy but subsequently relapsed (≥2 in 5). Clonal relationship between the diagnostic FL and relapses was confirmed in 11 cases. In 6 cases, common and distinct variants were seen between the paired diagnostic and relapsed lymphomas, indicating their divergent evolution from a CLP. In 2 cases, different Bcell clones were involved in the diagnostic and relapsed lymphomas, including 1 case involving 2 different BCL2 translocations. In the remaining 5 cases, the relapsed lymphoma developed via a linear progression (n=4) or a mixed evolutionary path (n=1). These findings may bear important implications in the routine diagnosis and management of relapsed FL.
Product Used
NGS

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