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

被引:21
作者
Carey, Christopher D. [1 ,2 ]
Gusenleitner, Daniel [3 ]
Chapuy, Bjoern [4 ]
Kovach, Alexandra E. [6 ]
Kluk, Michael J. [1 ]
Sun, Heather H. [1 ]
Crossland, Rachel E. [2 ]
Bacon, Chris M. [2 ]
Rand, Vikki [2 ]
Dal Cin, Paola [1 ]
Le, Long P. [6 ]
Neuberg, Donna [5 ]
Sohani, Aliyah R. [6 ]
Shipp, Margaret A. [4 ]
Monti, Stefano [3 ]
Rodig, Scott J. [1 ]
机构
[1] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[2] Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England
[3] Boston Univ, Sch Med, Dept Computat Med, Boston, MA 02118 USA
[4] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[5] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA
[6] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA
关键词
RITUXIMAB PLUS CYCLOPHOSPHAMIDE; THERAPEUTIC TARGETS; PROTEIN EXPRESSION; BURKITTS-LYMPHOMA; DISTINCT TYPES; MUTATIONS; BCL2; IDENTIFICATION; VINCRISTINE; DOXORUBICIN;
D O I
10.1016/j.jmoldx.2014.08.006
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
引用
收藏
页码:19 / 30
页数:12
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