Primary central nervous system lymphomas are derived from germinal-center B cells and show a preferential usage of the V4-34 gene segment

Citation
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
Journal title
AMERICAN JOURNAL OF PATHOLOGY
ISSN journal
00029440 → ACNP
Volume
155
Issue
6
Year of publication
1999
Pages
2077 - 2086
Database
ISI
SICI code
0002-9440(199912)155:6<2077:PCNSLA>2.0.ZU;2-H
Abstract
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.