title: Age dependent phosphorylation and deregulation of p53 in human vestibular schwannomas.
abstract: Tumor-specific alterations at the p53 gene locus in 30 human vestibular schwannomas (VS) comprising 10 confirmed NF2 cases and 20 sporadic cases were analyzed. We found loss of heterozygosity (LOH) at the first intron of the p53 gene locus in 54% of the informative cases. This is the first report showing LOH at the p53 gene locus in a significant number of human VS and both sporadic and NF2 cases show the LOH event. Increased levels of normal size p53 mRNA and p53 protein were found in all the tumors analyzed. Thus p53 appears to be deregulated in all the tumors suggesting that p53 alterations may be associated with tumor progression in VS. There was a negative significant correlation of patients' age and percentage of Ser 392 phosphorylated p53 protein. The tumor samples obtained from younger patients of 35 yr and below showed higher percentage of Ser 392 phosphorylated p53 protein compared to the tumors of older patients. The increased percentage of Ser 392 phosphorylated p53 protein indicates that it could be involved in the acceleration of tumor growth in the younger patients. Our results suggest that age dependent phosphorylation of p53 protein and deregulation of p53 gene has a role in the development of human vestibular schwannomas.
authors.affiliation: Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Antony H P P
authors.initials: AH
authors.lastname: Dayalan
authors.forename: Mathivanan
authors.initials: M
authors.lastname: Jothi
authors.forename: Rohini
authors.initials: R
authors.lastname: Keshava
authors.forename: Remy
authors.initials: R
authors.lastname: Thomas
authors.forename: Mohan L
authors.initials: ML
authors.lastname: Gope
authors.forename: Subbakrishna K
authors.initials: SK
authors.lastname: Doddaballapur
authors.forename: Sampath
authors.initials: S
authors.lastname: Somanna
authors.forename: Shanti S
authors.initials: SS
authors.lastname: Praharaj
authors.forename: Chandramouli B
authors.initials: CB
authors.lastname: Ashwathnarayanarao
authors.forename: Rajalakshmi
authors.initials: R
authors.lastname: Gope
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009464:Neuroma, Acoustic / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D012694:Serine / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D012694:Serine