Premium
Frequent inactivation of the tumor suppressor Kruppel‐like factor 6 ( KLF6 ) in hepatocellular carcinoma
Author(s) -
KremerTal Sigal,
Reeves Helen L.,
Narla Goutham,
Thung Swan N.,
Schwartz Myron,
Difeo Analisa,
Katz Amanda,
Bruix Jordi,
BioulacSage Paulette,
Martignetti John A.,
Friedman Scott L.
Publication year - 2004
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20460
Subject(s) - hepatocellular carcinoma , loss of heterozygosity , hccs , cancer research , tumor suppressor gene , cirrhosis , hepatitis b virus , biology , pathogenesis , hepatitis c virus , medicine , virus , cancer , gene , virology , immunology , carcinogenesis , genetics , allele
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. (H EPATOLOGY 2004;40:1047–1052.)