PMID- 21233831 OWN - NLM STAT- MEDLINE DCOM- 20110609 LR - 20151119 IS - 1476-5551 (Electronic) IS - 0887-6924 (Linking) VI - 25 IP - 4 DP - 2011 Apr TI - The isotype of the BCR as a surrogate for the GCB and ABC molecular subtypes in diffuse large B-cell lymphoma. PG - 681-8 LID - 10.1038/leu.2010.302 [doi] AB - 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. FAU - Ruminy, P AU - Ruminy P AD - INSERM U918, Laboratoire de genetique oncologique, Genetique et clinique des proliferations lymphoides, IFRMP23, Centre Henri Becquerel, Rouen, France. phirum@rouen.fnclcc.fr FAU - Etancelin, P AU - Etancelin P FAU - Couronne, L AU - Couronne L FAU - Parmentier, F AU - Parmentier F FAU - Rainville, V AU - Rainville V FAU - Mareschal, S AU - Mareschal S FAU - Bohers, E AU - Bohers E FAU - Burgot, C AU - Burgot C FAU - Cornic, M AU - Cornic M FAU - Bertrand, P AU - Bertrand P FAU - Lenormand, B AU - Lenormand B FAU - Picquenot, J-M AU - Picquenot JM FAU - Jardin, F AU - Jardin F FAU - Tilly, H AU - Tilly H FAU - Bastard, C AU - Bastard C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110114 PL - England TA - Leukemia JT - Leukemia JID - 8704895 RN - 0 (Biomarkers, Tumor) RN - 0 (Immunoglobulin Heavy Chains) RN - 0 (Immunoglobulin M) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Antigen, B-Cell) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - B-Lymphocytes/*pathology MH - Biomarkers, Tumor/genetics/metabolism MH - Female MH - Gene Expression Profiling MH - Germinal Center/*pathology MH - Humans MH - Immunoenzyme Techniques MH - Immunoglobulin Heavy Chains/genetics MH - Immunoglobulin M/genetics MH - In Situ Hybridization, Fluorescence MH - Lymphoma, Large B-Cell, Diffuse/*classification/*genetics MH - Male MH - Middle Aged MH - Oligonucleotide Array Sequence Analysis MH - RNA, Messenger/genetics MH - Receptors, Antigen, B-Cell/*genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Survival Rate EDAT- 2011/01/15 06:00 MHDA- 2011/06/10 06:00 CRDT- 2011/01/15 06:00 PHST- 2011/01/15 06:00 [entrez] PHST- 2011/01/15 06:00 [pubmed] PHST- 2011/06/10 06:00 [medline] AID - leu2010302 [pii] AID - 10.1038/leu.2010.302 [doi] PST - ppublish SO - Leukemia. 2011 Apr;25(4):681-8. doi: 10.1038/leu.2010.302. Epub 2011 Jan 14.