Accumulation of genetic changes during development and progression of hepatocellular carcinoma: Loss of heterozygosity on chromosome arm Ip occurs at an early stage of hepatocarcinogenesis
✍ Scribed by Tamobu Kuroki; Yoshiyuki Fujiwara; Eiju Tsuchiya; Shouji Nakamori; Shingi Imaoka; Takashi Kanematw; Yusuke Nakamura
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 424 KB
- Volume
- 13
- Category
- Article
- ISSN
- 1045-2257
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✦ Synopsis
To investigate cumulative genetic changes during development and progression of hepatocellular carcinoma (HCC), we examined DNAs isolated from I04 tumors for loss of heterozygosity (LOH) at I 3 loci on six chromosomal arms and for an increase of copy number ("multiplication") of alleles on 8q, using polymorphic microsatellite markers. A comparison of genetic features with clinicopathological stages of these tumors revealed that LOH on I p had occurred in tumors at an early stage or with a well-differentiated histological phenotype (W26 3 I %) as well as in tumors at more advanced stages. Genetic alterations on chromosome arms 4q. 8p, 8q, I 3q, I6q, and I7p were more often observed in tumors of more advanced stages and poorer differentiation grades. When size was the criterion for comparison, LOH on I p was observed frequently even in tumors smaller than 2 cm (6/ 16; 38%), whereas allelic losses on 16q were detected frequently only in larger tumors. These results suggest that the putative tumor suppressor gene(s) assumed t o be located on I p may be involved in an early step of carcinogenesis in liver tissue and that the other genetic alterations examined here may play important roles in progression of HCC. Genes Chrornosorn Cancer 13:/63-167 (1995). 0 1995 Wiley-Lin. Inc.