title: Mutated VH genes and preferential VH3-21 use define new subsets of mantle cell lymphoma.
abstract: Mantle cell lymphoma (MCL) is believed to originate from a naive B cell. However, we recently demonstrated that a subset of MCL displayed mutated V(H) genes. We also reported restricted use of certain V(H) genes. To assess the prognostic impact of these new findings, we performed V(H) gene analysis of 110 patients, revealing that 18 (16%) patients had mutated and 92 (84%) patients had unmutated V(H) genes. Because the mutation rate was low in the mutated group (2.2%-6.7%), further investigation of the germline V(H) gene in T cells from 5 patients with mutated V(H) genes was carried out; results showed that the unrearranged V(H) gene was identical to the published sequence. These data confirm that the base pair substitutions within the rearranged V(H) genes represent hypermutations, and indicate germinal center exposure. However, V(H) gene mutation status did not correlate with prognosis because there was no difference in clinical outcome between the unmutated and mutated groups. The most frequently used V(H) genes were V(H)3-21 (21 patients) and V(H)4-34 (19 patients). A novel finding was that V(H)3-21(+) MCL almost exclusively expressed lambda light chains and displayed highly restricted use of the V(lambda)3-19 gene. V(H)3-21(+) patients had longer median survival than the remaining patients (53 vs 34 months; P =.03), but they tended to be younger at diagnosis. The combined use of V(H)3-21/V(lambda)3-19 suggests a possible role for antigen(s) in the pathogenesis of these tumors and indicates that V(H)3-21(+) patients constitute a new MCL entity.
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Sweden.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Walsh
authors.forename: Mia
authors.initials: M
authors.lastname: Thorsélius
authors.forename: Anna
authors.initials: A
authors.lastname: Johnson
authors.forename: Ola
authors.initials: O
authors.lastname: Söderberg
authors.forename: Mats
authors.initials: M
authors.lastname: Jerkeman
authors.forename: Erik
authors.initials: E
authors.lastname: Björck
authors.forename: Inger
authors.initials: I
authors.lastname: Eriksson
authors.forename: Ulf
authors.initials: U
authors.lastname: Thunberg
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
authors.forename: Mats
authors.initials: M
authors.lastname: Ehinger
authors.forename: Eva
authors.initials: E
authors.lastname: Löfvenberg
authors.forename: Kristina
authors.initials: K
authors.lastname: Wallman
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.forename: Birgitta
authors.initials: B
authors.lastname: Sander
authors.forename: Anna
authors.initials: A
authors.lastname: Porwit-MacDonald
authors.forename: Michael
authors.initials: M
authors.lastname: Dictor
authors.forename: Tor
authors.initials: T
authors.lastname: Olofsson
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Göran
authors.initials: G
authors.lastname: Roos
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017931:DNA Primers; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D020522:Lymphoma, Mantle-Cell / Q000145:classification / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region