LIVER DISEASE INK4a-ARF alterations in liver cell adenoma
نویسندگان
چکیده
Background: The INK4a-ARF (CDKN2A) locus on chromosome 9p21 encodes two tumour suppressor proteins, p16 and p14, whose functions are inactivated in many human cancers. Aims: To evaluate p14 and p16 alterations in liver cell adenoma. Methods: After microdissection, DNA from 25 liver cell adenomas and corresponding normal liver tissue were analysed for INK4-ARF inactivation by DNA sequence analysis, methylation specific polymerase chain reaction, restriction enzyme related-polymerase chain reaction (RE-PCR), mRNA expression, microsatellite analysis, and immunohistochemistry. In addition, microdeletion of p14 and p16 were assessed by differential PCR. Results: Methylation of p14 was found in 3/25 cases (12%) and alterations in p16 occurred in 6/25 liver cell adenomas (24%) which correlated with loss of mRNA transcription. We failed to detect microdeletions or specific mutations of both exons. p16 methylation appeared in the context of an unmethylated p14 promoter in six cases. In normal liver tissue, p14 or p16 alterations were not observed. Conclusions: Our data suggest that p14 methylation occurs independently of p16 alterations in liver cell adenomas. Furthermore, methylation of p14 and p16 may be a result of cell cycle deregulation and does not seem to be a prerequisite of malignancy.
منابع مشابه
INK4a-ARF alterations in liver cell adenoma.
BACKGROUND The INK4a-ARF (CDKN2A) locus on chromosome 9p21 encodes two tumour suppressor proteins, p16(INK4a) and p14(ARF), whose functions are inactivated in many human cancers. AIMS To evaluate p14(ARF) and p16(INK4a) alterations in liver cell adenoma. METHODS After microdissection, DNA from 25 liver cell adenomas and corresponding normal liver tissue were analysed for INK4-ARF inactivati...
متن کاملMice with alterations in both p53 and Ink4a/Arf display a striking increase in lung tumor multiplicity and progression: differential chemopreventive effect of budesonide in wild-type and mutant A/J mice.
p53 transgenic mice carrying a dominant negative mutation were crossed with Ink4A/Arf heterozygous-deficient mice to investigate whether there is a synergy between these two germ-line mutations in promoting carcinogen-induced lung tumor progression in mice. Mice with a p53 dominant negative mutation and Ink4A/Arf heterozygous deficiency exhibited >20-fold increase in tumor volume compared with ...
متن کاملAlterations of the INK4a/ARF locus in human intracranial germ cell tumors.
Little is known about the molecular mechanisms responsible for the development of intracranial germ cell tumors (ICGTs). Recently, we demonstrated that the balance of the p53-mdm2 interactions is disrupted in ICGTs. The p14ARF product, a tumor suppresser gene located on the INK4a/ARF locus, acts as one of the major factors affecting p53-mdm2 interactions via its binding to mdm2 and the stimulat...
متن کاملBmi1 Is Required for Hepatic Progenitor Cell Expansion and Liver Tumor Development
Bmi1 is a polycomb group transcriptional repressor and it has been implicated in regulating self-renewal and proliferation of many types of stem or progenitor cells. In addition, Bmi1 has been shown to function as an oncogene in multiple tumor types. In this study, we investigated the functional significance of Bmi1 in regulating hepatic oval cells, the major type of bipotential progenitor cell...
متن کاملFine-mapping loss of gene architecture at the CDKN2B (p15INK4b), CDKN2A (p14ARF, p16INK4a), and MTAP genes in head and neck squamous cell carcinoma.
OBJECTIVE To identify the extent and the smallest region of loss for CDKN2B(INK4b), CDKN2A(ARF,INK4a), and MTAP. Homozygous deletions of human chromosome 9p21 occur frequently in malignant cell lines and are common in squamous cell carcinoma of the head and neck (HNSCC). This complex region encodes the tumor suppressor genes cyclin-dependent kinase 2B (CDKN2B) (p15(INK4b)) and CDKN2A (p14(ARF),...
متن کامل