Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnosed multiple myeloma.
Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnosed multiple myeloma.
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DOI：
10.1038/leu.2011.53
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发表时间：
2011-06
期刊：
影响因子：
11.4
通讯作者：
Fonseca, R.
中科院分区：
文献类型：
--
作者：
Chng, W-J;Huang, G. F.;Chung, T. H.;Ng, S. B.;Gonzalez-Paz, N.;Troska-Price, T.;Mulligan, G.;Chesi, M.;Bergsagel, P. L.;Fonseca, R.
从未确定意义的恶性前单克隆伽玛病（MGUS）向多发性骨髓瘤（MM）转变的介导事件尚不清楚。我们分析了在Affymetrix U133平台上生成的来自22例MGUS和101例MM患者的基因表达数据集，并使用基因集富集分析。MM中过表达的基因在细胞周期、增殖和MYC激活基因组中富集。在剖析MYC和细胞周期基因集之间的关系后，我们鉴定并验证了与增殖分离的MYC激活特征。应用这一特征，MYC在67%的骨髓瘤中被激活，但在MGUS中没有被激活。膜CD138和细胞核MYC双染色的免疫组化进一步证实了这一点。我们还发现，几乎所有RAS突变的肿瘤都表达MYC激活特征，并且MYC的激活可能涉及多种机制。MYC激活，无论是通过基因表达标记还是免疫组织化学来评估，都与超二倍体MM相关，即使在非增生性肿瘤中，生存期也较短。硼替佐米治疗能够克服MYC激活患者的生存劣势。
Events mediating transformation from the pre-malignant monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) are unknown. We analyzed a gene expression datasets generated on the Affymetrix U133 platform from 22 MGUS and 101 MM patients using gene-set enrichment analysis. Genes over-expressed in MM were enriched for cell cycle, proliferation and MYC activation gene-sets. Upon dissecting the relationship between MYC and cell cycle genesets, we identified and validated a MYC activation signature dissociated from proliferation. Applying this signature, MYC is activated in 67% of myeloma, but not in MGUS. This was further confirmed by immunohistochemistry using membrane CD138 and nuclear MYC double staining. We also showed that almost all tumors with RAS mutations expressed the MYC activation signature, and multiple mechanisms may be involved in activating MYC. MYC activation, whether assessed by gene expression signature or immunohistochemistry is associated with hyperdiploid MM, and shorter survival even in tumors that are not proliferative. Bortezomib treatment is able to overcome the survival disadvantage in patients with MYC activation.
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通讯作者：
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