Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP.

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Abstract

MYC dysregulation, including MYC gene rearrangement and Myc protein overexpression, is of increasing clinical importance in diffuse large B-cell lymphoma (DLBCL). However, the roles of MYC and the relative importance of rearrangement vs overexpression remain to be refined. Gaining knowledge about the tumor biology associated with MYC dysregulation is important to understand the roles of MYC and MYC-associated biology in lymphomagenesis. In this study, we determined MYC rearrangement status (n=344) and Myc expression (n=535) in a well-characterized DLBCL cohort, individually assessed the clinical and pathobiological features of patients with MYC rearrangement and Myc protein overexpression, and analyzed the prognosis and gene expression profiling signatures associated with these MYC abnormalities in germinal center B-cell-like and activated B-cell-like DLBCL. Our results showed that the prognostic importance of MYC rearrangement vs Myc overexpression is significantly different in germinal center B-cell-like vs activated B-cell-like DLBCL. In germinal center B-cell-like DLBCL, MYC-rearranged germinal center B-cell-like DLBCL patients with Myc overexpression significantly contributed to the clinical, biological, and prognostic characteristics of the overall Myc-overexpressing germinal center B-cell-like DLBCL group. In contrast, in activated B-cell-like DLBCL, the occurrence, clinical and biological features, and prognosis of Myc overexpression were independent of MYC rearrangement. High Myc levels and Myc-independent mechanisms, either tumor cell intrinsic or related to tumor microenvironment, conferred significantly worse survival to MYC-rearranged germinal center B-cell-like DLBCL patients, even among Myc(high)Bcl-2(high) DLBCL patients. This study provides new insight into the tumor biology and prognostic effects associated with MYC dysregulation and suggest that detection of both MYC translocations and evaluation of Myc and Bcl-2 expression is necessary to predict the prognosis of DLBCL patients.

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Journal

Journal ID (iso-abbrev): Mod. Pathol.

Title: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

Publisher: Springer Nature

ISSN (Electronic): 1530-0285

ISSN (Print): 0893-3952

Publication date (Electronic): Dec 2015

Volume: 28

Issue: 12

Affiliations

[1 ] Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

[2 ] Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

[3 ] Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

[4 ] University Hospital, Basel, Switzerland.

[5 ] San Bortolo Hospital, Vicenza, Italy.

[6 ] Aalborg University Hospital, Aalborg, Denmark.

[7 ] Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

[8 ] Weill Medical College of Cornell University, New York, NY, USA.

[9 ] The Methodist Hospital, Houston, TX, USA.

[10 ] Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA.

[11 ] University of North Carolina School of Medicine, Chapel Hill, NC, USA.

[12 ] Cleveland Clinic, Cleveland, OH, USA.

[13 ] University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China.

[14 ] Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

[15 ] Asan Medical Center, Ulsan University College of Medicine, Seoul, South Korea.

[16 ] San Raffaele H Scientific Institute, Milan, Italy.

[17 ] Odense University Hospital, Odense, Denmark.

[18 ] Gundersen Lutheran Health System, La Crosse, WI, USA.

[19 ] Zhejiang University School of Medicine, Second University Hospital, Hangzhou, China.

[20 ] Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

[21 ] Hospital Universitario Marqués de Valdecilla, Santander, Spain.

[22 ] Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

[23 ] The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, TX, USA.

Article

Publisher Item ID: modpathol2015118

DOI: 10.1038/modpathol.2015.118

PubMed ID: 26541272

SO-VID: ce61f277-f6b6-48eb-b946-e7d9b724bfc7

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