Originally published as JCO Early Release 10.1200/JCO.2008.16.1455 on July 21 2008

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Del(6)(q22) and BCL6 Rearrangements in Primary CNS Lymphoma Are Indicators of an Aggressive Clinical Course

Francois M. Cady, Brian Patrick O'Neill, Mark E. Law, Paul A. Decker, David M. Kurtz, Caterina Giannini, Alyx B. Porter, Paul J. Kurtin, Patrick B. Johnston, Ahmet Dogan, Ellen D. Remstein

From the Department of Pathology, CellNetix Pathology, Olympia, WA; and Departments of Laboratory Medicine and Pathology, Neurology, Internal Medicine, and Biostatistics, Mayo Clinic, Rochester, MN

Corresponding author: Ellen D. Remstein, MD, Mayo Clinic, 200 1st St SW, Rochester, MN 55905; e-mail: remstein.ellen{at}mayo.edu

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.

published online ahead of print at www.jco.org on July 21, 2008.

Supported in part by the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE; P50 CA97274), and by the Mayo SPORE in Brain Cancer (P50 CA108961); cores and shared resources were supported by the Cancer Center Support Grant No. P30 CA15083 to Mayo Clinic Cancer Center, a National Cancer Institute–designated Comprehensive Cancer Center.

Presented at the Annual Meetings of the United States and Canadian Academy of Pathology (March 24-30, 2007, San Diego, CA) and the American Society for Hematology (December 8-11, 2007, Atlanta, GA).

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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