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Molecular Classification of MYC-Driven B-Cell Lymphomas by Targeted Gene Expression Profiling of Fixed Biopsy Specimens

Lookup NU author(s): Dr Christopher Carey, Dr Rachel Crossland, Dr Christopher Bacon, Dr Vikki Rand

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) are aggressive tumors of mature B cells that are distinguished by a combination of histomorphological, phenotypic, and genetic features. A subset of B-cell lymphomas, however, has one or more characteristics that overlap BL and DLBCL, and are categorized as B-cell lymphoma unclassifiable, with features intermediate between BL and DLBCL (BCL-U). Molecular analyses support the concept that there is a biological continuum between BL and DLBCL that includes variable activity of MYC, an oncoprotein once thought to be only associated with BL, but now recognized as a major predictor of survival among patients with DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). We tested whether a targeted expression profiling panel could be used to categorize tumors as BL and DLBCL, resolve the molecular heterogeneity of BCL-U, and capture MYC activity using RNA from formalin-fixed, paraffin-embedded biopsy specimens. A diagnostic molecular classifier accurately predicted pathological diagnoses of BL and DLBCL, and provided more objective subclassification for a subset of BCL-U and genetic double-hit lymphomas as molecular BL or DLBCL. A molecular classifier of MYC activity correlated with MYC IHC and stratified patients with primary DLBCL treated with R-CHOP into high- and tow-risk groups. These results establish a framework for classifying and stratifying MYC-driven, aggressive, B-cell lymphomas on the basis of quantitative molecular profiting that is applicable to fixed biopsy specimens.


Publication metadata

Author(s): Carey CD, Gusenleitner D, Chapuy B, Kovach AE, Kluk MJ, Sun HH, Crossland RE, Bacon CM, Rand V, Dal Cin P, Le LP, Neuberg D, Sohani AR, Shipp MA, Monti S, Rodig SJ

Publication type: Article

Publication status: Published

Journal: Journal of Molecular Diagnostics

Year: 2015

Volume: 17

Issue: 1

Pages: 19-30

Print publication date: 01/01/2015

Online publication date: 07/11/2014

Acceptance date: 28/08/2014

Date deposited: 06/07/2017

ISSN (print): 1525-1578

ISSN (electronic): 1943-7811

Publisher: Elsevier Inc

URL: http://dx.doi.org/10.1016/j.jmoldx.2014.08.006

DOI: 10.1016/j.jmoldx.2014.08.006


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