Dayalan Antony H P P, Jothi Mathivanan, Keshava Rohini, Thomas Remy, Gope Mohan L, Doddaballapur Subbakrishna K, Somanna Sampath, Praharaj Shanti S, Ashwathnarayanarao Chandramouli B, Gope Rajalakshmi
Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India.
Mol Carcinog. 2006 Jan;45(1):38-46. doi: 10.1002/mc.20150.
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.
对30例人类前庭神经鞘瘤（VS）进行了分析，其中包括10例确诊的NF2病例和20例散发性病例，检测p53基因位点的肿瘤特异性改变。我们发现在54%的信息性病例中，p53基因位点的第一个内含子存在杂合性缺失（LOH）。这是第一份报告显示在大量人类VS中p53基因位点存在LOH，且散发性和NF2病例均出现了LOH事件。在所有分析的肿瘤中均发现正常大小的p53 mRNA和p53蛋白水平升高。因此，p53似乎在所有肿瘤中均发生失调，提示p53改变可能与VS的肿瘤进展相关。患者年龄与Ser 392磷酸化p53蛋白的百分比呈显著负相关。与老年患者的肿瘤相比，从35岁及以下年轻患者获取的肿瘤样本中Ser 392磷酸化p53蛋白的百分比更高。Ser 392磷酸化p53蛋白百分比的增加表明其可能参与了年轻患者肿瘤生长的加速。我们的结果提示，p53蛋白的年龄依赖性磷酸化和p53基因的失调在人类前庭神经鞘瘤的发生发展中起作用。
