Age dependent phosphorylation and deregulation of p53 in human vestibular schwannomas.
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.
Dayalan
Antony H P P
AH
Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India.
Jothi
Mathivanan
M
Keshava
Rohini
R
Thomas
Remy
R
Gope
Mohan L
ML
Doddaballapur
Subbakrishna K
SK
Somanna
Sampath
S
Praharaj
Shanti S
SS
Ashwathnarayanarao
Chandramouli B
CB
Gope
Rajalakshmi
R
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*
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D012694:Serine