VH Gene Sequences From Primary Central Nervous System Lymphomas Indicate Derivation From Highly Mutated Germinal Center B Cells With Ongoing Mutational Activity

摘要: Primary central nervous system lymphoma (PCNSL) represents 1% to 3% intracranial tumors. Most PCNSL are located in the brain, and 75% large B-cell lymphomas. The largest subgroup of these tumors contains cells that resemble centroblasts has been labelled diffuse centroblastic (polymorphous) lymphoma. To investigate cell origin clonal history tumors, we have analyzed VH gene 5 cases PCNSL, all confirmed by histological studies be Epstein-Barr virus (EBV)-negative, high-grade V4-34 VH4 family was used 4 cases. All VHgenes were found accumulated very high levels somatic mutation (14% 25%). In 3 cases, intraclonal nucleotide heterogeneity, including codon deletion some clones 1 case, observed, indicating genes still under influence hypermutation mechanism. Analysis distribution silent replacement mutations showed evidence for preservation immunoglobulin structure These results suggest that, although there is no germinal center formation brain tissue, derived from a B with features associated location environment.