Molecular classification of MYC-driven B-cell lymphomas by targeted gene expression profiling of fixed biopsy specimens.

Christopher D Carey, Daniel Gusenleitner, Bjoern Chapuy, Alexandra E Kovach, Michael J Kluk, Heather H Sun, Rachel E Crossland, Chris M Bacon, V Rand, Cin Paola Dal, Long P Le, Donna Neuberg, Aliyah R Sohani, Margaret A Shipp, Stefano Monti, Scott J Rodig

    Research output: Contribution to journalArticle

    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 low-risk groups. These results establish a framework for classifying and stratifying MYC-driven, aggressive, B-cell lymphomas on the basis of quantitative molecular profiling that is applicable to fixed biopsy specimens.
    Original languageEnglish
    Pages (from-to)19-30
    Number of pages12
    JournalJournal of Molecular Diagnostics
    Volume7
    Issue number1
    DOIs
    Publication statusPublished - 7 Nov 2014

    Fingerprint Dive into the research topics of 'Molecular classification of MYC-driven B-cell lymphomas by targeted gene expression profiling of fixed biopsy specimens.'. Together they form a unique fingerprint.

  • Cite this

    Carey, C. D., Gusenleitner, D., Chapuy, B., Kovach, A. E., Kluk, M. J., Sun, H. H., Crossland, R. E., Bacon, C. M., Rand, V., Dal, C. P., Le, L. P., Neuberg, D., Sohani, A. R., Shipp, M. A., Monti, S., & Rodig, S. J. (2014). Molecular classification of MYC-driven B-cell lymphomas by targeted gene expression profiling of fixed biopsy specimens. Journal of Molecular Diagnostics, 7(1), 19-30. https://doi.org/10.1016/j.jmoldx.2014.08.006