2014  0,718
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 51(2017) N 2 p. 293-299; DOI 10.1134/S0026893317020182 Full Text

P.P. Sarma1, D. Dutta2, Z. Mirza3, K.Kr. Saikia1*, B.Kr. Baishya2

Point mutations in the DNA binding domain of p53 contribute to glioma progression and poor prognosis

1Department of Bioengineering and Technology, Gauhati University, Guwahati, 781014 India
2Department of Neurosurgery, Gauhati Medical College and Hospital, Guwahati, 781026 India
3King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia

Received - 2015-12-31; Accepted - 2016-02-16

TP53 mutations play a significant role in glioma tumorigenesis. When located in in the DNA binding domain, these mutations can perturb p53 protein conformation and its function, often culminating in altered downstream signaling. Here we describe prevalent pattern of TP53 point mutations in a cohort of 40 glioma patients and show their relevance to gliomagenesis. Point mutations in exon 5-9 of TP53 gene were detected by DNA sequencing. Possible influence of identified mutations at the function of p53 was studied computationally and correlated with the survival. Point mutations in TP53 were detected in 10 glioma samples (25%), out of which 70% were from high grade glioma. A total of 19 TP53 point mutations were identified, out of which 42% were found to be in the DNA binding region of p53. Computational analysis predicted 87.5% of these mutations to be "probably damaging". In three patients with tumors possessing point mutations R273H, R248Q, Y163H and R175H and poor survival times, structural analysis revealed the nature of these mutations to be disruptive and associated with high risk for cancer progression. In high grade glioma, recurrent TP53 point mutations may be the key to tumor progression, thus, emphasizing their significance in gliomagenesis.

TP53, point mutations, high prevalence, glioma, malignancy, tumorigenesis, prognosis