Characterisation of Mutations In Exons 6 and 7 of the Tp53 Gene in Oral Squamous Cell Carcinoma in Kenya

Abstract

Background Oral squamous cell carcinoma (OSCC) is the commonest type of oral cancer accounting for over 96% of all reported oral cancer cases. GLOBOCAN 2012 reports the prevalence of lip and oral cavity cancer in Kenya to be more than 7.1 cases per 100,000 population. This is one of the highest prevalence rates in Africa. In Kenya oral cancer is reported to account for 3.6% of all cancers, with a slight male predominance. Onyango and colleagues in 2004 reported that OSCC accounted for 95% of all oral cancer in Kenya. Mutation or functional inactivation of the tumour suppressor gene TP53 is an almost universal feature of all human cancers. Mutant TP53 results in the coding of p53 protein that has lost its tumour suppressive properties thus allowing damaged DNA to progress through the cell cycle unchecked. The end result is continued propagation of cancerous cells. Prevalence rates of TP53 mutations have been reported from 16-96% while the International Agency for Research on Cancer (IARC) puts the prevalence at 42%. The commonest mutation type reported is the missense mutation at 75% of all mutations. Over 200 single nucleotide polymorphisms (SNPs) have been reported in literature. Only 1 SNP has been reported in the DNA binding domain (DBD). Study objective The broad objective was to characterise the mutations in exons 6 and 7 of TP53 gene in OSCC reported at a university teaching hospital in Nairobi, Kenya. Study design This was a cross-sectional descriptive laboratory based study including all OSCC reported and archived as paraffin-embedded tissue blocks in the years 2012 and 2013. Study setting The histopathology laboratory at the University of Nairobi Dental Hospital (UoNDH) provided paraffin-embedded tissue blocks for DNA extraction while DNA analysis for mutations was carried out at the molecular laboratory of the University of Nairobi Centre for Biotechnology and Bioinformatics (CEBIB). DNA sequencing was done at Inqaba Biotechnical Industries (Pty) Ltd.