title: The isotype of the BCR as a surrogate for the GCB and ABC molecular subtypes in diffuse large B-cell lymphoma.
abstract: Gene expression profiling has identified two major molecular subtypes of diffuse large B-cell lymphoma (DLBCL) that are histologically indistinguishable but differ in cure rates. Here, we investigated whether the isotype of the B-cell receptor (BCR) expressed by the tumoral cells correlated with the molecular subtype and survival. Gene expression analysis clustered the 53 patients included in this study into three subgroups, 17 germinal center B-cell-like (GCB) cases, 26 activated B-cell-like (ABC) cases and 10 intermediate cases. The molecular subtype was correlated with the isotype, as 15/17 GCB cases expressed a secondary isotype (immunoglobulin (Ig)G or IgA), whereas 24/26 ABC cases expressed a primary isotype (IgM or IgD) (P<0.0001). There was a trend toward a worse outcome for patients with an ABC DLBCL and a shorter overall survival for patients with IgM+ tumor (P=0.21 and 0.014, respectively). Finally, fluorescence in situ hybridization (FISH) analysis revealed a striking asymmetric pattern, as the IGHM gene is conserved only on the productive IGH allele in most IgM+ tumors. Taken together, these data indicate that the isotype of the BCR is a reliable indicator for the GCB and ABC subtypes in DLBCL, and suggest that the conservation of an IgM is required for ABC DLBCL lymphomagenesis to occur.
authors.affiliation: INSERM U918, Laboratoire de génétique oncologique, Génétique et clinique des proliférations lymphoïdes, IFRMP23, Centre Henri Becquerel, Rouen, France. phirum@rouen.fnclcc.fr
authors.forename: P
authors.initials: P
authors.lastname: Ruminy
authors.forename: P
authors.initials: P
authors.lastname: Etancelin
authors.forename: L
authors.initials: L
authors.lastname: Couronné
authors.forename: F
authors.initials: F
authors.lastname: Parmentier
authors.forename: V
authors.initials: V
authors.lastname: Rainville
authors.forename: S
authors.initials: S
authors.lastname: Mareschal
authors.forename: E
authors.initials: E
authors.lastname: Bohers
authors.forename: C
authors.initials: C
authors.lastname: Burgot
authors.forename: M
authors.initials: M
authors.lastname: Cornic
authors.forename: P
authors.initials: P
authors.lastname: Bertrand
authors.forename: B
authors.initials: B
authors.lastname: Lenormand
authors.forename: J-M
authors.initials: JM
authors.lastname: Picquenot
authors.forename: F
authors.initials: F
authors.lastname: Jardin
authors.forename: H
authors.initials: H
authors.lastname: Tilly
authors.forename: C
authors.initials: C
authors.lastname: Bastard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell