Molecular histogenesis of plasmablastic lymphoma of the oral cavity.
Plasmablastic lymphoma (PBL) of the oral cavity is an aggressive B-cell lymphoma associated with human immunodeficiency virus infection. Although the lymphoma phenotype is consistent with late B-cell maturation, the molecular histogenesis of PBL is unknown. We investigated PBL of the oral cavity (n = 12) for mutations of immunoglobulin variable heavy chain (IgVH) and BCL-6 genes, which are acquired by B cells at the time of germinal centre (GC) transit, and for expression of BCL-6, MUM-1 and CD138, which distinguish GC B cells from post-GC B cells. Somatic IgVH hypermutation occurred in 4/10 PBL whereas 6/10 PBL displayed germline IgVH genes. Among PBL carrying hypermutated IgVH genes, the pattern of IgVH mutations was consistent with antigen stimulation in two cases. Mutations of the BCL-6 gene were restricted to 1/12 patients with PBL of the oral cavity. All cases of PBL of the oral cavity displayed the BCL-6-/MUM-1+/CD138+ phenotype that is consistent with late stage of B-cell differentiation. Overall, these data indicate that, despite a common phenotype and an apparently similar degree of differentiation, PBL of the oral cavity are characterized by histogenetic heterogeneity. A subset of PBL of the oral cavity carried the molecular clues of GC transit and conceivably originated from a B-cell subset corresponding to post-GC B cells. Conversely, another fraction of these lymphomas were devoid of somatic IgVH mutations and appeared to originate from naive B cells that have undergone preterminal differentiation independent of GC transit.
Gaidano
Gianluca
G
Hematology Unit, Division of Internal Medicine, Department of Medical Sciences, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy. gaidano@med.unipmn.it
Cerri
Michaela
M
Capello
Daniela
D
Berra
Eva
E
Deambrogi
Clara
C
Rossi
Davide
D
Larocca
Luigi Maria
LM
Campo
Elias
E
Gloghini
Annunziata
A
Tirelli
Umberto
U
Carbone
Antonino
A
D000328:Adult; D004268:DNA-Binding Proteins / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000235:genetics; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D050835:Interferon Regulatory Factors; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D011509:Proteoglycans / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors / Q000235:genetics; D000099218:Interferon Regulatory Factor-4
D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D050835:Interferon Regulatory Factors; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C508241:SDC1 protein, human