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Blood, 1 July 2001, Vol. 98, No. 1, pp. 238-240
BRIEF REPORT
Variable heavy-chain gene analysis of follicular lymphomas:
subclone selection rather than clonal evolution over time
Wilhelmina M. Aarts,
Richard J. Bende,
Janneke G. Bossenbroek,
Steven T. Pals, and
Carel J. M. van
Noesel
From the Department of Pathology, Academic Medical
Center, Amsterdam, The Netherlands.
To investigate B-cell receptor evolution in follicular lymphomas
(FLs), immunoglobulin variable heavy chain (VH) gene
regions of 3 FLs were analyzed at different time points. One FL with a high somatic mutation load and intraclonal VH gene
diversity was investigated in situ. VH gene transcripts
were amplified and sequenced from samples of approximately 50 tumor
cells isolated from frozen tissue sections by laser microdissection.
Interestingly, the mutation pattern of the prevalent subclone in the
relapse biopsy was virtually identical to that of a subclone isolated
by microdissection from the presentation biopsy 9 years earlier. In a
second FL, proof was obtained that the subclone that dominated the
relapse sample had already been present in the initial biopsy. The
finding that subclones found in the relapses of these FLs had not
evolved over time but were preexistent, challenges the concept of
antigen-driven B-cell receptor evolution during disease course.
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