Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma.
Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma.
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DOI：
10.1309/ajcp2z0tagmuyjeb
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发表时间：
2013-02
影响因子：
3.5
通讯作者：
Rimsza L
中科院分区：
文献类型：
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作者：
Valentino C;Kendrick S;Johnson N;Gascoyne R;Chan WC;Weisenburger D;Braziel R;Cook JR;Tubbs R;Campo E;Rosenwald A;Ott G;Delabie J;Jaffe E;Zhang W;Brunhoeber P;Nitta H;Grogan T;Rimsza L
8号染色体上MYC癌基因的缺失是伯基特淋巴瘤和其他侵袭性B细胞淋巴瘤（包括弥漫性大B细胞淋巴瘤（DLBCL））的特征。我们最近描述了一种比色原位杂交（CISH）方法，用于检测DLBCL中MYC基因的额外拷贝，以及在8号染色体的二倍体或多倍性背景下频繁发生的离散MYC信号的过量拷贝，这与mRNA信号增加相关。我们进一步观察到放大的MYC信号，其被计数为单个基因拷贝，但根据其尺寸和不寻常的形状，可能由MYC基因的“簇”组成。在这项研究中，我们试图通过确定这些信号的存在是否与其他遗传特征，mRNA水平，蛋白质和总生存率相关来进一步表征这些MYC信号簇。我们发现MYC簇与异常MYC基因座和mRNA增加相关。MYC mRNA与蛋白质水平相关，mRNA和蛋白质的增加与总生存率降低相关。在DLBCL的生发中心和活化的B细胞亚型中都观察到MYC簇。MYC信号簇可能是侵袭性B细胞淋巴瘤的一个未被充分认识但具有临床重要性的特征，具有潜在的预后和治疗相关性。
Abnormalities of the MYC oncogene on chromosome 8 are characteristic of Burkitt lymphoma and other aggressive B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We recently described a colorimetric in situ hybridization (CISH) method for detecting extra copies of the MYC gene in DLBCL and the frequent occurrence of excess copies of discrete MYC signals in the context of diploidy or polyploidy of chromosome 8, which correlated with increased mRNA signals. We further observed enlarged MYC signals, which were counted as a single gene copy but, by their dimension and unusual shape, likely consisted of “clusters” of MYC genes. In this study, we sought to further characterize these clusters of MYC signals by determining whether the presence of these correlated with other genetic features, mRNA levels, protein, and overall survival. We found that MYC clusters correlated with an abnormal MYC locus and with increased mRNA. MYC mRNA correlated with protein levels, and both increased mRNA and protein correlated with poorer overall survival. MYC clusters were seen in both the germinal center and activated B-cell subtypes of DLBCL. Clusters of MYC signals may be an underappreciated, but clinically important, feature of aggressive B-cell lymphomas with potential prognostic and therapeutic relevance.