PURPOSE: Primary CNS lymphoma (PCNSL) is an aggressive lymphoma but clinically validated biologic markers that can predict natural history to tailor treatment according to risk are lacking. Several genetic changes including BCL6 rearrangements and deletion of 6q22, containing the putative tumor suppressor gene PTPRK, are potential risk predictors. Herein we determined the prevalence and survival impact of del(6)(q22) and BCL6, immunoglobulin heavy chain (IGH), and MYC gene rearrangements in a large PCNSL cohort treated in a single center. PATIENTS AND METHODS: Interphase fluorescence in situ hybridization was performed using two-color probes for BCL6, MYC, IGH-BCL6, and del(6)(q22) on thin sections of 75 paraffin-embedded samples from 75 HIV-negative, immunocompetent patients newly diagnosed with PCNSL. Survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and proportional hazards regression adjusting for age, deep structure involvement, and high-dose methotrexate (HDMTX) treatment. RESULTS: The prevalence of del(6)(q22) and BCL6, IGH, and MYC translocations was 45%,17%, 13%, and 3%, respectively. The presence of del(6)(q22) and/or a BCL6 translocation was associated with inferior overall survival (OS; P = .0097). The presence of either del(6)(q22) alone or a BCL6 translocation alone was also associated with inferior OS (P = .0087). Univariable results held after adjusting for age, deep structure involvement, and HDMTX. CONCLUSION: Del (6)(q22) and BCL6 rearrangements are common in PCNSL and predict for decreased OS independent of deep structure involvement and HDMTX. Unlike systemic diffuse large B-cell lymphoma, del(6)(q22) is common and IGH translocations are infrequent and usually involve BCL6 rather than BCL2, suggesting a distinct pathogenesis.
PURPOSE:Primary CNS lymphoma (PCNSL) is an aggressive lymphoma but clinically validated biologic markers that can predict natural history to tailor treatment according to risk are lacking. Several genetic changes including BCL6 rearrangements and deletion of 6q22, containing the putative tumor suppressor gene PTPRK, are potential risk predictors. Herein we determined the prevalence and survival impact of del(6)(q22) and BCL6, immunoglobulin heavy chain (IGH), and MYC gene rearrangements in a large PCNSL cohort treated in a single center. PATIENTS AND METHODS: Interphase fluorescence in situ hybridization was performed using two-color probes for BCL6, MYC, IGH-BCL6, and del(6)(q22) on thin sections of 75 paraffin-embedded samples from 75 HIV-negative, immunocompetent patients newly diagnosed with PCNSL. Survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and proportional hazards regression adjusting for age, deep structure involvement, and high-dose methotrexate (HDMTX) treatment. RESULTS: The prevalence of del(6)(q22) and BCL6, IGH, and MYC translocations was 45%,17%, 13%, and 3%, respectively. The presence of del(6)(q22) and/or a BCL6 translocation was associated with inferior overall survival (OS; P = .0097). The presence of either del(6)(q22) alone or a BCL6 translocation alone was also associated with inferior OS (P = .0087). Univariable results held after adjusting for age, deep structure involvement, and HDMTX. CONCLUSION: Del (6)(q22) and BCL6 rearrangements are common in PCNSL and predict for decreased OS independent of deep structure involvement and HDMTX. Unlike systemic diffuse large B-cell lymphoma, del(6)(q22) is common and IGH translocations are infrequent and usually involve BCL6 rather than BCL2, suggesting a distinct pathogenesis.
Authors: C Bastard; C Deweindt; J P Kerckaert; B Lenormand; A Rossi; F Pezzella; C Fruchart; C Duval; M Monconduit; H Tilly Journal: Blood Date: 1994-05-01 Impact factor: 22.113
Authors: Andres Alonso; Joanna Sasin; Nunzio Bottini; Ilan Friedberg; Iddo Friedberg; Andrei Osterman; Adam Godzik; Tony Hunter; Jack Dixon; Tomas Mustelin Journal: Cell Date: 2004-06-11 Impact factor: 41.582
Authors: F Lo Coco; B H Ye; F Lista; P Corradini; K Offit; D M Knowles; R S Chaganti; R Dalla-Favera Journal: Blood Date: 1994-04-01 Impact factor: 22.113
Authors: Javeed Iqbal; Warren G Sanger; Douglas E Horsman; Andreas Rosenwald; Diane L Pickering; Bhavana Dave; Sandeep Dave; Li Xiao; Kajia Cao; Quiming Zhu; Simon Sherman; Christine P Hans; Dennis D Weisenburger; Timothy C Greiner; Randy D Gascoyne; German Ott; H Konrad Müller-Hermelink; Jan Delabie; Rita M Braziel; Elaine S Jaffe; Elias Campo; James C Lynch; Joseph M Connors; Julie M Vose; James O Armitage; Thomas M Grogan; Louis M Staudt; Wing C Chan Journal: Am J Pathol Date: 2004-07 Impact factor: 4.307
Authors: David H George; Bernd W Scheithauer; Fügen V Aker; Paul J Kurtin; Peter C Burger; José Cameselle-Teijeiro; Roger E McLendon; Joseph E Parisi; Werner Paulus; Wolfgang Roggendorf; Cirilo Sotelo Journal: Am J Surg Pathol Date: 2003-04 Impact factor: 6.394
Authors: Rachel M Lynch; Sudhir Naswa; Gary L Rogers; Stephen A Kania; Suchita Das; Elissa J Chesler; Arnold M Saxton; Michael A Langston; Brynn H Voy Journal: Physiol Genomics Date: 2010-02-23 Impact factor: 3.107
Authors: Esteban Braggio; Scott Van Wier; Juhi Ojha; Ellen McPhail; Yan W Asmann; Jan Egan; Jackline Ayres da Silva; David Schiff; M Beatriz Lopes; Paul A Decker; Riccardo Valdez; Raoul Tibes; Bruce Eckloff; Thomas E Witzig; A Keith Stewart; Rafael Fonseca; Brian Patrick O'Neill Journal: Clin Cancer Res Date: 2015-05-19 Impact factor: 12.531
Authors: Esteban Braggio; Ellen Remstein McPhail; William Macon; M Beatriz Lopes; David Schiff; Mark Law; Stephanie Fink; Debra Sprau; Caterina Giannini; Ahmet Dogan; Rafael Fonseca; Brian Patrick O'Neill Journal: Clin Cancer Res Date: 2011-05-11 Impact factor: 12.531
Authors: I Vater; M Montesinos-Rongen; M Schlesner; A Haake; F Purschke; R Sprute; N Mettenmeyer; I Nazzal; I Nagel; J Gutwein; J Richter; I Buchhalter; R B Russell; O D Wiestler; R Eils; M Deckert; R Siebert Journal: Leukemia Date: 2014-09-05 Impact factor: 11.528