Genetic analysis of the LKB1/STK11 gene in hepatocellular carcinomas

被引:48
作者
Kim, CJ [1 ]
Cho, YG [1 ]
Park, JY [1 ]
Kim, TY [1 ]
Lee, JH [1 ]
Kim, HS [1 ]
Lee, JW [1 ]
Song, YH [1 ]
Nam, SW [1 ]
Lee, SH [1 ]
Yoo, NJ [1 ]
Lee, JY [1 ]
Park, WS [1 ]
机构
[1] Catholic Univ Korea, Coll Med, Dept Pathol, Seocho Gu, Seoul 137701, South Korea
关键词
STK1; /LKB1; p53; mutation; loss of heterozygosity; apoptosis; hepatocellular carcinoma;
D O I
10.1016/S0959-8049(03)00659-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The tumour suppressor gene, LKB1/STK11, has been mapped to chromosome 19p13, a region showing frequent allelic loss in various human cancers, including hepatocellular carcinoma (HCC). Additionally, LKB1 physically associates with p53 and regulates p53-dependent apoptotic pathways. To investigate whether genetic alterations of LKB1 could be involved in the tumorigenesis of HCC, we analysed the genetic alterations of the LKB1 and p53 genes in seven dysplastic nodules and 80 HCCs. We found one LKB1 missense mutation, CCG--> CTG (Pro--> Leu) at codon 281 within the kinase domain. We also found allelic loss in six of 27 (22%) informative HCC cases and all of them were HBV-positive cases. In addition, we detected seven missense, one nonsense and one silent mutations (nine of 80, 11%) of p53 in HCCs only. These results suggest that genetic alterations of the LKB1 or p53 genes may play an important role in tumour development or progression of a sub-set of HCCs, and may also provide alternative mechanisms to protect the HCC cell from p53-dependent apoptosis. (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码:136 / 141
页数:6
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