Möröy T, Marchio A, Etiemble J, Trépo C, Tiollais P, Buendia M A
Nature. 1986;324(6094):276-9. doi: 10.1038/324276a0.
Hepatocellularcarcinoma (HCC) that occur in woodchucks chronically infected with woodchuck hepatitis virus (WHV) were screened for activation of cellular oncogenes. Enhanced expression and allelic alterations of the c-myc oncogene were found in three HCC out of nine. Variations in the size of the c-myc transcripts, ranging from 2.0 kilobases (kb) to 5.6 kb, as well as in the level of c-myc gene expression, 5-50-fold higher than in adjacent liver tissues, were observed among the three HCC. Rearrangements of the c-myc locus were either upstream of the gene or within the first intron. Cloning and sequencing of the break-point region from one of the three tumours showed that the c-myc gene was truncated and joined to a unique cellular sequence of unknown function. WHV DNA was not integrated near the c-myc coding exons, excluding a direct role of the virus in c-myc activation. The novel type of rearrangement and activation of the c-myc gene, reported here in liver tumours of hepatitis virus infected animals, appears strikingly similar to those resulting from chromosomal translocations in human Burkitt's lymphomas, acute B- and T-cell leukaemias and mouse plasmacytomas.
对慢性感染土拨鼠肝炎病毒（WHV）的土拨鼠所患肝细胞癌（HCC）进行细胞癌基因激活筛查。在9例HCC中，有3例发现c-myc癌基因表达增强和等位基因改变。在这3例HCC中，观察到c-myc转录本大小从2.0千碱基（kb）到5.6 kb不等，以及c-myc基因表达水平比相邻肝组织高5至50倍。c-myc基因座的重排要么在基因上游，要么在第一个内含子内。对这3个肿瘤之一的断点区域进行克隆和测序表明，c-myc基因被截断并与一个功能未知的独特细胞序列相连。WHV DNA未整合在c-myc编码外显子附近，排除了病毒在c-myc激活中的直接作用。本文报道的肝炎病毒感染动物肝肿瘤中c-myc基因的新型重排和激活，与人类伯基特淋巴瘤、急性B细胞和T细胞白血病以及小鼠浆细胞瘤中染色体易位导致的情况惊人相似。
