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Blood, Vol. 94 No. 5 (September 1), 1999:
pp. 1738-1746
VH Gene Sequences From Primary Central Nervous System
Lymphomas Indicate Derivation From Highly Mutated Germinal Center B
Cells With Ongoing Mutational Activity
Andrew R. Thompsett,
David W. Ellison,
Freda K. Stevenson, and
Delin Zhu
From the Molecular Immunology Group, Tenovus Research Laboratory and
the Department of Pathology (Neuropathology), Southampton University
Hospitals Trust, Southampton, UK.
Primary central nervous system lymphoma (PCNSL) represents 1% to
3% intracranial tumors. Most PCNSL are located in the brain, and 75%
are large B-cell lymphomas. The largest subgroup of these tumors
contains cells that resemble centroblasts and has been labelled diffuse
centroblastic (polymorphous) lymphoma. To investigate the cell of
origin and the clonal history of these tumors, we have analyzed
VH gene of 5 cases of PCNSL, all confirmed by histological studies to be Epstein-Barr virus (EBV)-negative,
high-grade diffuse B-cell lymphomas. The V4-34 gene of the
VH4 family was used in 4 of 5 cases. All VH
genes were found to have accumulated very high levels of somatic
mutation (14% to 25%). In 3 of 5 cases, intraclonal nucleotide
heterogeneity, including codon deletion in some clones in 1 case, was
observed, indicating that the VH genes were still under the
influence of the somatic hypermutation mechanism. Analysis of the
distribution of silent and replacement mutations showed evidence for
preservation of immunoglobulin structure in all cases. These results
suggest that, although there is no evidence for germinal center
formation in the brain tissue, PCNSL is derived from a B cell with
features associated with location in a germinal center environment.
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