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Frequent inactivation of the tumor suppressor Kruppel-like factor 6 (KLF6) in hepatocellular carcinoma

Lookup NU author(s): Professor Helen ReevesORCiD

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Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, reflecting incomplete characterization of underlying mechanisms and lack of early detection. Krüppel-like factor 6 (KLF6) is a ubiquitously expressed zinc finger transcription factor that is deregulated in multiple cancers through loss of heterozygosity (LOH) and/or inactivating somatic mutation. We analyzed the potential role of the KLF6 tumor suppressor gene in 41 patients who had HCC associated with hepatitis C virus (16 patients), hepatitis B virus (12 patients, one of whom was coinfected with hepatitis C virus), and other etiologies (14 patients) by determining the presence of LOH and mutations. Overall, LOH and/or mutations were present in 20 (49%) of 41 tumors. LOH of the KLF6 gene locus was present in 39% of primary HCCs, and the mutational frequency was 15%. LOH and/or mutations were distributed across all etiologies of HCC evaluated, including patients who did not have cirrhosis. Functionally, wild-type KLF6 decreased cellular proliferation of HepG2 cells, while patient-derived mutants did not. In conclusion, we propose that KLF6 is deregulated by loss and/or mutation in HCC, and its inactivation may contribute to pathogenesis in a significant number of these tumors.

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Author(s): Kremer-Tal, S., Reeves, H. L., Narla, G., Thung, S., Schwartz, M., Difeo, A., Katz, A., Bruix, J., Bioulac-Sage, P., Martignetti, J., Friedman, S.

Publication type: Article

Publication status: Published

Journal: Hepatology

Year: 2004

Volume: 40

Issue: 5

Pages: 1047-1052

Print publication date: 01/11/2004

ISSN (print): 0270-9139

ISSN (electronic): 1527-3350

URL: http://dx.doi.org/10.1002/hep.20460

DOI: 10.1002/hep.20460

PubMed id: 15486921

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