Raidl Maria, Pirker Christine, Schulte-Hermann Rolf, Aubele Michaela, Kandioler-Eckersberger Daniela, Wrba Fritz, Micksche Michael, Berger Walter, Grasl-Kraupp Bettina
Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
J Hepatol. 2004 Apr;40(4):660-8. doi: 10.1016/j.jhep.2003.12.020.
BACKGROUND/AIMS: In human hepatocarcinogenesis the tumor precursor lesions and the sequence of genetic aberrations are not known. We therefore compared genetic alterations of different types of benign liver lesions to those of hepatocellular carcinoma.
By comparative genomic hybridisation (CGH) 40 cases, including cirrhotic liver (CL), focal nodular hyperplasia (FNHs), hepatocellular adenoma (HCAs), dysplastic nodules (DNs), primary hepatocellular carcinoma (HCCs), and hepatocellular metastases to the lung were studied.
FNHs and HCAs exhibited few chromosomal abnormalities. Frequency and pattern of genetic alterations in DNs highly resembled those in HCCs: gains of DNA clustered in chromosome arms 1p/q, 7q, 15q, 16p, 17q, and 20q and losses were often found at 3p, 4q, 9p, and 11q. Aberrations on 1p, 6q, 8p/q, and 13q occurred almost exclusively in HCCs; the gain at 8q encompassed amplification of c-myc, as verified by fluorescence in situ hybridisation.
The pattern of genetic alterations in HCCs resembled more the alterations found in DNs than in FNHs and HCAs, suggesting that DNs may be the actual tumor precursors. Furthermore, alterations at 4q, 9p, 11q, 16p, and 17q appear as early genetic events being crucial for hepatocarcinogenesis.
背景/目的：在人类肝癌发生过程中，肿瘤前体病变以及基因畸变序列尚不清楚。因此，我们比较了不同类型良性肝损伤与肝细胞癌的基因改变情况。
通过比较基因组杂交（CGH）研究了40例病例，包括肝硬化肝（CL）、局灶性结节性增生（FNHs）、肝细胞腺瘤（HCAs）、发育异常结节（DNs）、原发性肝细胞癌（HCCs）以及肝转移至肺的病例。
FNHs和HCAs显示出很少的染色体异常。DNs中基因改变的频率和模式与HCCs高度相似：DNA增益集中在染色体臂1p/q、7q,、15q、16p、17q和20q，缺失常发生在3p、4q、9p和11q。1p、6q、8p/q和13q上的畸变几乎仅发生在HCCs中；8q处的增益包括c-myc的扩增，这通过荧光原位杂交得到证实。
HCCs中的基因改变模式与DNs中发现的改变比FNHs和HCAs中的更相似，这表明DNs可能是实际的肿瘤前体。此外，4q、9p、11q、16p和17q处的改变似乎是对肝癌发生至关重要的早期基因事件。
