Show simple item record

dc.contributor.authorFreedberg, D.E.*
dc.contributor.authorRigas, S.H.*
dc.contributor.authorRussak, J.*
dc.contributor.authorGai, W.*
dc.contributor.authorKaplow, M.*
dc.contributor.authorOsman, I.*
dc.contributor.authorTurner, F.*
dc.contributor.authorRanderson-Moor, J.A.*
dc.contributor.authorHoughton, A.*
dc.contributor.authorBusam, K.*
dc.contributor.authorBishop, D.T.*
dc.contributor.authorBastian, B.C.*
dc.contributor.authorNewton-Bishop, J.A.*
dc.contributor.authorPolsky, D.*
dc.date.accessioned2014-04-28T09:55:03Z
dc.date.available2014-04-28T09:55:03Z
dc.date.issued2008
dc.identifier.citationFreedberg DE, Rigas SH, Russak J et al (2008) Frequent p16-independent inactivation of p14ARF in human melanoma. Journal of the National Cancer Institute. 100(11): 784-795.
dc.identifier.urihttp://hdl.handle.net/10454/5973
dc.description.abstractBACKGROUND: The tumor suppressors p14(ARF) (ARF) and p16(INK4A) (p16) are encoded by overlapping reading frames at the CDKN2A/INK4A locus on chromosome 9p21. In human melanoma, the accumulated evidence has suggested that the predominant tumor suppressor at 9p21 is p16, not ARF. However, recent observations from melanoma-prone families and murine melanoma models suggest a p16-independent tumor suppressor role for ARF. We analyzed a group of melanoma metastases and cell lines to investigate directly whether somatic alterations to the ARF gene support its role as a p16-independent tumor suppressor in human melanoma, assuming that two alterations (genetic and/or epigenetic) would be required to inactivate a gene. METHODS: We examined the p16/ARF locus in 60 melanoma metastases from 58 patients and in 9 human melanoma cell lines using multiplex ligation-dependent probe amplification and multiplex polymerase chain reaction (PCR) to detect deletions, methylation-specific PCR to detect promoter methylation, direct sequencing to detect mutations affecting ARF and p16, and, in a subset of 20 tumors, immunohistochemistry to determine the effect of these alterations on p16 protein expression. All statistical tests were two-sided. RESULTS: We observed two or more alterations to the ARF gene in 26/60 (43%) metastases. The p16 gene sustained two or more alterations in 13/60 (22%) metastases (P = .03). Inactivation of ARF in the presence of wild-type p16 was seen in 18/60 (30%) metastases. CONCLUSION: Genetic and epigenetic analyses of the human 9p21 locus indicate that modifications of ARF occur independently of p16 inactivation in human melanoma and suggest that ARF is more frequently inactivated than p16.
dc.relation.isreferencedbyhttp://dx.doi.org/10.1093/jnci/djn157
dc.subjectAnimals
dc.subject; Cell line; Tumor
dc.subject; Chromosomes; Pair 9
dc.subject; DNA methylation
dc.subject; Gene deletion
dc.subject; Gene silencing
dc.subject; Genes; p16
dc.subject; Humans
dc.subject; Immunoblotting
dc.subject; Immunohistochemistry
dc.subject; Melanoma; Genetics; Pathology
dc.subject; Mice
dc.subject; Microsatellite repeats
dc.subject; Mutation
dc.subject; Neoplasm proteins
dc.subject; Polymerase chain reaction
dc.subject; Promoter regions
dc.subject; Tumor suppressor protein p14ARF
dc.subject; REF 2014
dc.titleFrequent p16-independent inactivation of p14ARF in human melanoma
dc.typeArticle


This item appears in the following Collection(s)

Show simple item record