title: Tumor cell dissemination in follicular lymphoma.
abstract: The derivation of follicular lymphomas (FLs) from germinal centers is not only supported by their morphologic appearance with a nodular growth pattern and a germinal center-like cellular composition, but also by the presence of ongoing somatic hypermutation (a germinal center B cell-specific process) during their clonal expansion. The intraclonal sequence diversity of the tumor cells and their follicular growth pattern allows one to analyze lymphoma cell dissemination and the way the tumor "metastasizes" to distinct follicles. In the present study, we analyzed individual follicles of 3 FLs by micromanipulation of single cells from individual lymphoma follicles and amplification of immunoglobulin V region genes. Genealogical trees for the V(H) and the V(L) gene rearrangements were constructed to analyze the clonal relationship among individual cells of 3 distinct follicles of each case. In all 3 cases there is evidence that distinct tumor follicles are founded by many tumor cells, suggesting that there is extensive migration of the tumor cells among follicles. The observation that the tumor cells of FLs retain their follicular growth patterns despite this cellular migration supports the idea that they depend on the follicular microenvironment for their clonal expansion.
authors.affiliation: Senckenberg Department of Pathology, University of Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. oeschger@em.uni-frankfurt.de
authors.forename: Sabine
authors.initials: S
authors.lastname: Oeschger
authors.forename: Andreas
authors.initials: A
authors.lastname: Bräuninger
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
mesh_terms: D002465:Cell Movement; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D015321:Gene Rearrangement; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000032:analysis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000032:analysis / Q000235:genetics; D008198:Lymph Nodes / Q000473:pathology; D008224:Lymphoma, Follicular / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region