title: Translocations involving the immunoglobulin heavy chain gene locus predict better survival in gastric diffuse large B-cell lymphoma.
abstract: OBJECTIVE
  The pathogenesis and clinical heterogeneity of gastric diffuse large B-cell lymphoma (DLBCL) are poorly understood. We have comprehensively investigated the incidence and clinical significance of lymphoma-associated chromosomal translocations, particularly those involving the immunoglobulin heavy chain (IGH) gene locus, in a large series of gastric DLBCL.
  
  
  METHODS
  One hundred forty-one cases of primary gastric DLBCL [58 with mucosa-associated lymphoid tissue (MALT) lymphoma and 83 without MALT lymphoma] were enrolled. Translocations involving BCL6, c-MYC, FOXP1, MALT1, and IGH were investigated using interphase fluorescence in situ hybridization. In positive cases, additional fluorescence in situ hybridization was done with appropriate probes for potential partner genes. Cases were classified into germinal center B-cell-like (GCB) or non-GCB subgroups by immunophenotyping with CD10, BCL6, and MUM1.
  
  
  RESULTS
  Translocations involving IGH were detected in 36 (32%) of 111 cases; their partner genes included BCL6 (n = 10), c-MYC (n = 5), and FOXP1 (n = 3) but remained unknown in the remaining 18 cases. t(14;18)/IGH-BCL2, t(14;18)/IGH-MALT1, and t(1;14)/BCL10-IGH were not detected in any case. t(11;18)/API2-MALT1 was detected in none of the cases, except for one case of DLBCL with MALT lymphoma, which showed positive signals only in MALT lymphoma cells. IGH-involved translocation was associated with younger age but not with any other clinicopathologic factors including GCB or non-GCB immunophenotypes. Cox multivariate analysis revealed that IGH-involved translocation, in addition to younger age and early stage, was an independent prognostic factor for better overall and EFSs.
  
  
  CONCLUSIONS
  IGH-involved translocations are frequent in gastric DLBCL and seem to identify cases with favorable prognosis.
authors.affiliation: Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom. shonaka@intmed2.med.kyushu-u.ac.jp
authors.forename: Shotaro
authors.initials: S
authors.lastname: Nakamura
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ye
authors.forename: Chris M
authors.initials: CM
authors.lastname: Bacon
authors.forename: Alison
authors.initials: A
authors.lastname: Goatly
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Liu
authors.forename: Lucy
authors.initials: L
authors.lastname: Kerr
authors.forename: Alison H
authors.initials: AH
authors.lastname: Banham
authors.forename: Berthold
authors.initials: B
authors.lastname: Streubel
authors.forename: Takashi
authors.initials: T
authors.lastname: Yao
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tsuneyoshi
authors.forename: Antonella
authors.initials: A
authors.lastname: Savio
authors.forename: Morishige
authors.initials: M
authors.lastname: Takeshita
authors.forename: Peggy
authors.initials: P
authors.lastname: Dartigues
authors.forename: Agnès
authors.initials: A
authors.lastname: Ruskoné-Fourmestraux
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Iida
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Du
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality; D014178:Translocation, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains