An early lesion in hepatic carcinogenesis: loss of heterozygosity in human cirrhotic livers and dysplastic nodules at the 1p36-p34 region.
An early lesion in hepatic carcinogenesis: loss of heterozygosity in human cirrhotic livers and dysplastic nodules at the 1p36-p34 region.
复制标题
肝癌发生的早期病变：人肝硬化肝脏杂合性丧失和 1p36-p34 区域发育不良结节。
DOI：
10.1053/jhep.2001.24751
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Sudilovsky,O
中科院分区：
文献类型：
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作者：
Sun,M;Eshleman,JR;Ferrell,LD;Jacobs,G;Sudilovsky,EC;Tuthill,R;Hussein,MR;Sudilovsky,O
染色体组型分析表明，1号染色体杂合性缺失（洛杂合性缺失）是人类肝癌发生的初始阶段。然而，这种改变尚未在结核性结节（CN）或发育不良结节（DN）中进行研究。在一项来自切除或切除的肝硬化的初步研究中，在31例肝细胞癌（HCC）、25例低度异型增生结节（LGDN）和24例高度异型增生结节（HGDN）中检测了1 p36-p32的洛缺失。在HCC中，洛缺失最常见的位点是D1 S2843（1 p36. 1）（28.6%），D1S513（1p34. 3）（29.2%）和MYCL 1（1 p34. 1例（28.6%）。在HGDN和LGDN中，D1 S513位点的洛丢失率分别为11.1%和13.6%。为了进一步完善这些结果并确定CN、DN和HCC之间的顺序关系，接下来在另外53个HCC、56个HGDN、30个LGDN和215个CN中研究了洛，这些CNs来自11个切除的人类肝组织，包括30个“结节中结节”病变。D1S2843（1p36. 12)和MYCL 1（1 p34. 1），和1个各在D1 S484（1 q24. 1）、IGF 2 R-3（6 q26）和TP 53（17 p13. 1)用了D1 S2843和D1 S513的洛分别在HCC（20.4%和23.5%）、HGDN（7.7%和18.5%）、LGDN（13.6%和6.9%）和HCC或DN周围的CN（7.4%和8.3%）中检测到。这些结果表明D1 S2843和D1 S513位点的洛缺失是人类肝癌发生的早期事件。来自HCC或DN周围CN以及结节中结节病变的数据提供了支持CN→ DN→ HCC进展的证据。多个HCC和DN的不同缺失模式提示同一个体中癌发生的独立起源。
Loss of heterozygosity (LOH) of chromosome 1 has been suggested, by karyotyping, to be an initial episode in human hepatocarcinogenesis. However, this alteration has not yet been investigated in cirrhotic nodules (CNs) or dysplastic nodules (DNs). In an initial study from explanted or resected cirrhotic livers, LOH in 1p36–p32 was examined in 31 hepatocellular carcinomas (HCCs), 25 low–grade dysplastic nodules (LGDNs), and 24 high–grade dysplastic nodules (HGDNs). In HCCs, LOH was detected most frequently at loci D1S2843 (1p36. 1)(28.6%), D1S513 (1p34. 3)(29.2%), and MYCL1 (1p34. 1)(28.6%). In HGDN and LGDN, LOH incidences at D1S513 were 11.1% and 13.6%, respectively. To further refine those results and to determine sequential relationships among CN, DN, and HCC, LOH was next studied in an additional 53 HCCs, 56 HGDNs, 30 LGDNs, and 215 CNs from 11 explanted human cirrhotic livers, including 30 “nodule–in–nodule” lesions. Seven markers between D1S2843 (1p36. 12) and MYCL1 (1p34. 1), and 1 each at D1S484 (1q24. 1), IGF2R–3 (6q26), and TP53 (17p13. 1) were used. LOH at D1S2843 and D1S513 was detected in HCCs (20.4% and 23.5%, respectively), HGDNs (7.7% and 18.5%), LGDNs (13.6% and 6.9%), and CNs surrounding either HCCs or DNs (7.4% and 8.3%). These results demonstrate that LOH at D1S2843 and D1S513 are early events in human liver carcinogenesis. Data from CN surrounding either HCCs or DN, and also nodule–in–nodule lesions, provide evidence supporting a CN→ DN→ HCC progression. Different deletion patterns from multiple HCCs and DNs suggest independent origins for carcinogenesis in the same individual.