Maesako Yoshitomo, Uchiyama Takashi, Ohno Hitoshi
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Cancer Sci. 2003 Sep;94(9):774-81. doi: 10.1111/j.1349-7006.2003.tb01518.x.
To determine the specific gene expression in B-cell lymphoma subtypes, we compared expression profiles of cell lines from transformed follicular lymphoma (tFL), Epstein-Barr virus-negative (EBV(-)) Burkitt's lymphoma (BL) and EBV(+)BL. Complementary DNAs were synthesized from these cell lines and hybridized with the Atlas Human 1.2 Array membrane. Hierarchical clustering analysis based upon the levels of 43 genes highlighted characteristic expression patterns of the 3 lymphoma subtypes. Genes expressed at higher levels in tFL than EBV(-)BL and EBV(+)BL included calcium/calmodulin-dependent protein kinase I (CAMK1) and mitogen-activated protein kinase 10 (MAPK10). EBV(-)BL was characterized by high-level expression of amyloid beta precursor protein (APP), heat shock 27 kD protein 1 (HSPB1) and mothers against decapentaplegic homolog 1 (MADH1). Gardner-Rasheed feline sarcoma viral oncogene homolog (FGR) was the most significant gene to delineate EBV(+)BL. A subtype prediction algorithm using 34 genes correctly classified 22 (92%) of 24 lymphomas into FL/tFL, EBV(-)BL or EBV(+)BL. By comparison with normal reference B-cell materials, the expression patterns of the selected genes were characteristic of lymphomas. We extended the clustering analysis to cell lines from de novo diffuse large B-cell lymphoma (DLBCL). The DLBCL cell lines were either separated from the former 3 lymphoma subtypes or segregated with EBV(+)BL, possibly reflecting variable genetic abnormalities. The associations of CAMK1 with tFL, APP and MADH1 with EBV(-)BL, FGR with EBV(+)BL, and BCL2 with tFL and DLBCL were confirmed by real-time quantitative reverse transcriptase-mediated polymerase chain reaction assays. This study has provided new molecular markers, expressions of which are closely associated with B-cell lymphoma subtypes.
为了确定B细胞淋巴瘤亚型中的特定基因表达，我们比较了转化型滤泡性淋巴瘤（tFL）、爱泼斯坦-巴尔病毒阴性（EBV(-)）伯基特淋巴瘤（BL）和EBV(+)BL细胞系的表达谱。从这些细胞系中合成互补DNA，并与Atlas Human 1.2 Array膜杂交。基于43个基因水平的层次聚类分析突出了这3种淋巴瘤亚型的特征性表达模式。在tFL中表达水平高于EBV(-)BL和EBV(+)BL的基因包括钙/钙调蛋白依赖性蛋白激酶I（CAMK1）和丝裂原活化蛋白激酶10（MAPK10）。EBV(-)BL的特征是β淀粉样前体蛋白（APP）、热休克27kD蛋白1（HSPB1）和母亲对十二烷基体同源物1（MADH1）的高水平表达。加德纳-拉希德猫肉瘤病毒癌基因同源物（FGR）是区分EBV(+)BL的最显著基因。使用34个基因的亚型预测算法将24个淋巴瘤中的22个（92%）正确分类为FL/tFL、EBV(-)BL或EBV(+)BL。与正常参考B细胞材料相比，所选基因的表达模式是淋巴瘤的特征。我们将聚类分析扩展到原发性弥漫性大B细胞淋巴瘤（DLBCL）的细胞系。DLBCL细胞系要么与前3种淋巴瘤亚型分离，要么与EBV(+)BL聚集在一起，这可能反映了不同的基因异常。通过实时定量逆转录介导的聚合酶链反应分析证实了CAMK1与tFL、APP和MADH1与EBV(-)BL、FGR与EBV(+)BL以及BCL2与tFL和DLBCL之间的关联。本研究提供了新的分子标志物，其表达与B细胞淋巴瘤亚型密切相关。
