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[A candidate tumor suppressor gene mutated in primary hepatocellular carcinoma: kruppel-like factor 6]
Shao-ping Wang1, Xiao-ping Chen, Fa-zu Qiu
1Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Objective:
To explore the relationship between kruppel-like factor (KLF)6 gene and the development or progression of hepatocellular carcinoma (HCC).
Methods:
Reverse-transcription polymerase chain reaction (RT-PCR) was used to examine the expression of KLF6 mRNA in normal liver tissue and primary hepatocellular carcinoma, and single strand conformation polymorphism (SSCP), DNA sequencing were used to detect the point mutation of KLF6 in primary hepatocellular carcinoma.
Results:
An amplified fragment of 427 bp DNA was detected in 31 (97%) of 32 adjacent noncancerous tissue and normal liver tissue, and in 23 (85%) of 27 HCCs. There was no significant difference in the levels of KLF6 mRNA between normal liver and liver tumors (chi(2) = 2.58, P > 0.05). For the 27 HCCs, six SSCP-positive bands (22%) were detected. Among them, three of 5 (3/5) tumor samples showing loss of heterozygosity (LOH) of KLF6 had mutations in the retained KLF6 allele.
Conclusion:
We showed that LOH was detected in 5 (36%) HCCs obtained from 14 informative cases, and three of 5 tumor samples showing LOH of KLF6 had mutations in the retained KLF6 allele. Two inactivating events had occurred; thus, as defined by Knudson's "two-hit model", 16 KLF6 appears to be a tumor suppressor gene.
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