The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Genetic and epigenetic alterations of the INK4a-ARF pathway in cholangiocarcinoma.

The INK4a-ARF locus, located on chromosome 9p21, encodes two cell-cycle regulatory proteins, p16(INK4a) and p14(ARF), acting through the Rb-CDK4 and p53 pathways. To study the contribution of each pathway in the tumourigenesis of cholangiocarcinoma, the alterations of p14(ARF), p16(INK4a), p53, and pRb were analysed. After microdissection, DNAs from 51 cholangiocarcinomas were analysed by methylation-specific PCR (MSP), restriction-enzyme related polymerase chain reaction (RE-PCR), microsatellite analysis, mRNA expression, and DNA sequencing. Immunohistochemistry of p14(ARF), p16(INK4a), p53, and pRb was also performed. Promoter methylation of p14(ARF) was found in 13/51 cases (25%) and p16(INK4a) showed aberrant promoter methylation in 39/51 cases (76%) which correlated with loss of mRNA transcription. Two tumours (4%) had homozygous deletion of the INK4a-ARF locus. Specific mutations of both exons were not detected. p14(ARF) inactivation appeared in the context of an unmethylated p16(INK4a) promoter in eight of 13 cases (61%) of the carcinomas methylated at p14(ARF). Mutations of p53 were found in 19 of 51 tumours (37%), and four of them (21%) harboured p14(ARF) inactivation. The pRb protein was detected in 30/51 (59%) tumours examined. The absence of pRB protein did not correlate with any of the examined parameters. Alterations of the INK4a-ARF locus, pRB or p53 status could not be established as independent prognostic factors in these tumours. These findings indicate that the INK4a-ARF locus is frequently inactivated in cholangiocarcinoma of the liver and occurs independently of the status of p53 or pRb.[1]

References

  1. Genetic and epigenetic alterations of the INK4a-ARF pathway in cholangiocarcinoma. Tannapfel, A., Sommerer, F., Benicke, M., Weinans, L., Katalinic, A., Geissler, F., Uhlmann, D., Hauss, J., Wittekind, C. J. Pathol. (2002) [Pubmed]
 
WikiGenes - Universities