Department of Pathology, University of Arizona College of Medicine, Tucson, 85724, USA.
Am J Clin Pathol. 2013 Feb;139(2):242-54. doi: 10.1309/AJCP2Z0TAGMUYJEB.
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.
8 号染色体上 MYC 癌基因的异常是 Burkitt 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用于检测 DLBCL 中 MYC 基因额外拷贝的比色原位杂交（CISH）方法，以及在 8 号染色体二倍体或多倍体背景下离散 MYC 信号的频繁过量，这与 mRNA 信号的增加相关。我们进一步观察到 MYC 信号增大，这些信号被计为单个基因拷贝，但从其尺寸和异常形状来看，可能由“簇”的 MYC 基因组成。在这项研究中，我们试图通过确定这些簇是否与其他遗传特征、mRNA 水平、蛋白质和总生存率相关，进一步对这些 MYC 信号簇进行特征描述。我们发现 MYC 簇与异常的 MYC 基因座和增加的 mRNA 相关。MYC mRNA 与蛋白水平相关，mRNA 和蛋白均增加与总体生存率较差相关。在生发中心和激活 B 细胞亚型的 DLBCL 中均可见 MYC 信号簇。MYC 信号簇可能是侵袭性 B 细胞淋巴瘤中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。
