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
Tamobu Kuroki
Department of Biochemistry, Cancer Institute, Tokyo, Japan
Search for more papers by this authorYoshiyuki Fujiwara
Department of Biochemistry, Cancer Institute, Tokyo, Japan
Search for more papers by this authorEiju Tsuchiya
Department of Pathology, Cancer Institute, Tokyo, Japan
Search for more papers by this authorShouji Nakamori
Department of Surgery, The Center for Adult Disease, Osaka, Japan
Search for more papers by this authorShingi Imaoka
Department of Surgery, The Center for Adult Disease, Osaka, Japan
Search for more papers by this authorTakashi Kanematw
The Second Department of Surgery, Nagasaki University School of Medicine, Nagasaki, Japan
Search for more papers by this authorCorresponding Author
Yusuke Nakamura MD,PhD
Department of Biochemistry, Cancer Institute, Tokyo, Japan
Laboratoy of Molecular Medicine, Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo 108, JapanSearch for more papers by this authorTamobu Kuroki
Department of Biochemistry, Cancer Institute, Tokyo, Japan
Search for more papers by this authorYoshiyuki Fujiwara
Department of Biochemistry, Cancer Institute, Tokyo, Japan
Search for more papers by this authorEiju Tsuchiya
Department of Pathology, Cancer Institute, Tokyo, Japan
Search for more papers by this authorShouji Nakamori
Department of Surgery, The Center for Adult Disease, Osaka, Japan
Search for more papers by this authorShingi Imaoka
Department of Surgery, The Center for Adult Disease, Osaka, Japan
Search for more papers by this authorTakashi Kanematw
The Second Department of Surgery, Nagasaki University School of Medicine, Nagasaki, Japan
Search for more papers by this authorCorresponding Author
Yusuke Nakamura MD,PhD
Department of Biochemistry, Cancer Institute, Tokyo, Japan
Laboratoy of Molecular Medicine, Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo 108, JapanSearch for more papers by this authorAbstract
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 (8/26 31 %) 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 to 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. © 1995 Wiley-Liss, Inc.
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