title: Molecular heterogeneity in MCL defined by the use of specific VH genes and the frequency of somatic mutations.
abstract: This study explores whether the presence of somatic mutations or a biased use of IgV(H) genes were associated with the clinical features in a series of 96 patients with mantle cell lymphoma (MCL). The cases were studied by seminested polymerase chain reaction using primers from the FR1 and J(H) regions. There was an unexpectedly high frequency of somatic mutations, with 29 of 103 sequences showing more than 2% of mutations. Biased usage of specific V(H) segments was also found; the most widely used genes in this series were V(H)3-21 (10 cases), V(H)3-23 (9 cases), V(H)4-34 (11 cases), and V(H)4-59 (9 cases). V(H) mutation frequency, taking into account different thresholds, did not distinguish different overall survival probabilities. Nevertheless, a more frequent use of V(H)3-21 or V(H)4-59 (8 of 18) was observed in the group of long-term survivors (18 cases > 5 years; P <.01). None of these long-term survivors presented the V(H)3-23 gene rearrangement. As in other lymphoproliferative disorders, the expression of CD38 or p53 or both was associated with a poorer survival probability. This nonrandom usage of IgV(H) segments suggests that specific antigens may play a pathogenically relevant role in the genesis or progression of subsets of MCL cases and may help in distinguishing a significant group of MCL long-term survivors.
authors.affiliation: Centro Nacional de Investigaciones Oncológicas, Molecular Pathology Program, Madrid, Spain.
authors.forename: Francisca I
authors.initials: FI
authors.lastname: Camacho
authors.forename: Patrocinio
authors.initials: P
authors.lastname: Algara
authors.forename: Antonia
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Elena
authors.initials: E
authors.lastname: Ruíz-Ballesteros
authors.forename: Manuela
authors.initials: M
authors.lastname: Mollejo
authors.forename: Nerea
authors.initials: N
authors.lastname: Martínez
authors.forename: José A
authors.initials: JA
authors.lastname: Martínez-Climent
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Marisol
authors.initials: M
authors.lastname: Mateo
authors.forename: Alessia
authors.initials: A
authors.lastname: Caleo
authors.forename: Margarita
authors.initials: M
authors.lastname: Sánchez-Beato
authors.forename: J
authors.initials: J
authors.lastname: Menárguez
authors.forename: Javier
authors.initials: J
authors.lastname: García-Conde
authors.forename: Francesc
authors.initials: F
authors.lastname: Solé
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007150:Immunohistochemistry; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region