title: Immunoglobulin heavy chain gene analysis of ocular adnexal extranodal marginal zone B-cell lymphoma.
abstract: OBJECTIVE
  To clarify the cellular origin of extranodal marginal-zone B-cell lymphoma (EZML) of the mucosa-associated lymphoid tissue (MALT) type in ocular adnexa, the somatic mutation was analyzed in the immunoglobulin heavy-chain variable region (VH) gene.
  
  
  METHODS
  Eight cases of EZML in the orbit and four in the conjunctiva were studied. The VH genes were amplified by a seminested PCR and sequenced directly. These were compared with the closest published VH germline segments to determine the somatic mutation frequency. Intraclonal microheterogeneity, which was termed the ongoing mutation frequency in the current study, was estimated by counting the number of single nucleotide substitutions in individual clones and dividing by the total number of nucleotides analyzed. Nine cases of gastrointestinal EMZL were also examined for comparison.
  
  
  RESULTS
  The somatic mutation frequency varied between 2.0% and 12.7%, with a mean value of 7.9%. Ten cases with intraclonal microheterogeneity showed between one and six further substitutions. The average of ongoing mutation frequency was 0.11%, with a range of 0% to 0.25%. In the gastrointestinal EMZLs, the average of somatic mutation frequency was 8.5% (1.5%-14.2%) and of ongoing mutation frequency was 0.51% (0.25%-0.75%).
  
  
  CONCLUSIONS
  The average of ongoing mutation frequency in ocular adnexal EMZL was lower than that in gastrointestinal EMZL. Both ocular adnexal and gastrointestinal EMZLs are derived from postgerminal center memory B cells, but the low ongoing mutation frequencies of ocular adnexal EMZL may result from less antigen stimulation and follicular colonization in the orbit relative to gastrointestinal EMZL.
authors.affiliation: Department of Pathology, Fukushima Medical University School of Medicine, Fukushima-City, Japan. yhara@fmu.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
authors.forename: N
authors.initials: N
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Kuze
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: A
authors.initials: A
authors.lastname: Shirakawa
authors.forename: M
authors.initials: M
authors.lastname: Furuta
authors.forename: K
authors.initials: K
authors.lastname: Yago
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Abe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D003230:Conjunctival Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009918:Orbital Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains