title: Primary cutaneous B-cell lymphoma is associated with somatically hypermutated immunoglobulin variable genes and frequent use of VH1-69 and VH4-59 segments.
abstract: BACKGROUND
  Accurate assessment of the somatic mutational status of clonal immunoglobulin variable region (IgV) genes is relevant in elucidating tumour cell origin in B-cell lymphoma; virgin B cells bear unmutated IgV genes, while germinal centre and postfollicular B cells carry mutated IgV genes. Furthermore, biases in the IgV repertoire and distribution pattern of somatic mutations indicate a possible antigen role in the pathogenesis of B-cell malignancies.
  
  
  OBJECTIVE
  This work investigates the cellular origin and antigenic selection in primary cutaneous B-cell lymphoma (PCBCL).
  
  
  METHODS
  We analysed the nucleotide sequence of clonal IgV heavy-chain gene (IgVH) rearrangements in 51 cases of PCBCL (25 follicle centre, 19 marginal zone and seven diffuse large B-cell lymphoma, leg-type) and compared IgVH sequences with their closest germline segment in the GenBank database. Molecular data were then correlated with histopathological features.
  
  
  RESULTS
  We showed that all but one of the 51 IgVH sequences analysed exhibited extensive somatic hypermutations. The detected mutation rate ranged from 1.6% to 21%, with a median rate of 9.8% and was independent of PCBCL histotype. Calculation of antigen-selection pressure showed that 39% of the mutated IgVH genes displayed a number of replacement mutations and silent mutations in a pattern consistent with antigenic selection. Furthermore, two segments, VH1-69 (12%) and VH4-59 (14%), were preferentially used in our case series.
  
  
  CONCLUSIONS
  Data indicate that neoplastic B cells of PBCBL have experienced germinal centre reaction and also suggest that the involvement of IgVH genes is not entirely random in PCBCL and that common antigen epitopes could be pathologically relevant in cutaneous lymphomagenesis.
authors.affiliation: Istituto Dermopatico Dell'Immacolata-Istituto di Ricerca e Cura a Carattere Scientifico, Rome 00167, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Perez
authors.forename: A
authors.initials: A
authors.lastname: Pacchiarotti
authors.forename: M
authors.initials: M
authors.lastname: Frontani
authors.forename: E
authors.initials: E
authors.lastname: Pescarmona
authors.forename: E
authors.initials: E
authors.lastname: Caprini
authors.forename: G A
authors.initials: GA
authors.lastname: Lombardo
authors.forename: G
authors.initials: G
authors.lastname: Russo
authors.forename: T
authors.initials: T
authors.lastname: Faraggiana
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics* / Q000276:immunology; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics* / Q000276:immunology
chemical_list: D007135:Immunoglobulin Variable Region