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J Mol Diagn. 2015 Jan;17(1):19-30. doi: 10.1016/j.jmoldx.2014.08.006. Epub 2014 Nov 7.

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

Author information

1
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts; Northern Institute for Cancer Research, Newcastle Upon Tyne, United Kingdom.
2
Department of Computational Medicine, Boston University School of Medicine, Boston, Massachusetts.
3
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
4
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
5
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
6
Northern Institute for Cancer Research, Newcastle Upon Tyne, United Kingdom.
7
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
8
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: srodig@partners.org.

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.

PMID:
25468432
PMCID:
PMC4279427
DOI:
10.1016/j.jmoldx.2014.08.006
[Indexed for MEDLINE]
Free PMC Article

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