M. Montesinos-rongen et al., Primary central nervous system lymphomas are derived from germinal-center B cells and show a preferential usage of the V4-34 gene segment, AM J PATH, 155(6), 1999, pp. 2077-2086
Citations number
57
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Primary central nervous system lymphomas (PCNSLs) have recently received co
nsiderable clinical attention due to their increasing incidence, To clarify
the histogenetic origin of these intriguing neoplasms, PCNSLs from 10 HIV-
negative patients were analyzed for immunoglobulin (Ig) gene rearrangements
. All tumors exhibited clonal IgH gene rearrangements. Of the 10 cases, 5 u
sed the V4-34 gene segment, and all of these lymphomas shared an amino acid
exchange from glycine to aspartate due to a mutation in the first codon of
the complementarity-determining region 1, No preferential usage of D-H,J(H
), V-kappa, J(kappa), V-lambda, or J(lambda) gene segments was observed. Al
l potentially functional rearrangements exhibited somatic mutations. The pa
ttern of somatic mutations indicated selection of the tumor cells (or their
precursors) for expression of a functional antibody. Mean mutation frequen
cies of 13.2%and 8.3% were detected for the heavy and light chains, respect
ively, thereby exceeding other lymphoma entities. Cloning experiments of th
ree tumors showed ongoing mutation in at least one case. These data suggest
that PCNSLs are derived from highly mutated germinal-center B cells. The f
requent usage of the V4-34 gene and the presence of a shared replacement mu
tation may indicate that the tumor precursors' recognized a shared (super)
antigen.