Assessment of differentiation and progression of hepatic tumors using array-based comparative genomic hybridization

被引:47
作者
Steinemann, Doris
Skawran, Britta
Becker, Thomas
Tauscher, Marcel
Weigmann, Anja
Wingen, Luzie
Tauscher, Sarah
Hinrichsen, Tanja
Hertz, Sabine
Flemming, Peer
Flik, Jacobus
Wiese, Birgit
Kreipe, Hans
Lichter, Peter
Schlegelberger, Brigitte
Wilkens, Ludwig
机构
[1] Hannover Med Sch, Inst Cell & Mol Pathol, D-30625 Hannover, Germany
[2] Hannover Med Sch, Inst Pathol, D-30625 Hannover, Germany
[3] Hannover Med Sch, Dept Visceral & Transplantat Surg, D-30625 Hannover, Germany
[4] Hannover Med Sch, Inst Virol, D-30625 Hannover, Germany
[5] Hannover Med Sch, Inst Biometry, D-30625 Hannover, Germany
[6] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany
关键词
D O I
10.1016/j.cgh.2006.07.010
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Alms: To gain more information about the molecular mechanisms leading to dedifferentiation of hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC), high-resolution array-based comparative genomic hybridization (array-CGH) was performed on 24 cases of HCC and 10 cases of HCA. Methods: DNA chips containing 6251 individual bacterial artificial chromosome/plasmid artificial chromosome clones were used. They allowed for a genome-wide resolution of 1 Mb and an even higher resolution of up to 100 kb for chromosome regions recurrently involved in human tumors and for regions containing known tumor-suppressor genes and oncogenes. Results: Copy number changes on the genomic scale were found by array-based comparative genomic hybridization in all cases. In HCC, gains of chromosomal regions 1q (91.6%), and 8q (58.3%), and losses of 8p (54%) were found most frequently. Hierarchic cluster analysis branched all HCA from HCC. However, in 2 adenomas with a known history of glycogenosis type I and adenomatosis hepatis gains of 1q were found, too. The critically gained region was narrowed down to bands 1q22-23. Although no significant differences in the mean number of chromosomal aberrations were seen between adenomas and well-differentiated carcinomas (2.7 vs 4.6), a significant increase accompanied the dedifferentiation of HCC (14.1 in HCC-G2 and 16.3 in HCC-G2/3; P < .02). Dedifferentiation of HCC also was correlated closely to losses of 4q and 13q (P < .001 and < .005, respectively). Conclusions: The increased chromosomal instability during dedifferentiation of HCC leads to an accumulation of structural chromosomal aberrations and losses and gains of defined chromosome regions.
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页码:1283 / 1291
页数:9
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