Microsatellite instability in D2S123 flanking the hMSH2 gene in oral squamous cell carcinoma in South India

Abstract

Background: Oral cancer is the third most common cancer in India. It is a multifactorial disease. Cells with defective mismatch repair gene hMSH2 can result in genomic instability in oral squamous cell carcinoma (OSCC) tumors. The objective of this study was to investigate the incidence of microsatellite instability (MSI) flanking the hMSH2 in OSCC tumors and relate the MSI status with the mutation profile of hMSH2 in Malayalam speaking population from Kerala. Materials and Methods: Patients diagnosed with OSCC, without superimposed premalignant and other malignant conditions, were recruited for the study based on strict selection criteria. 37 subjects from Malayalam speaking ethnic background of Kerala in India were selected. Blood and carcinoma tissues from were obtained from each patient diagnosed with OSCC. Big adenine tract 26 (BAT26) and D2S123 microsatellite flanking the hMSH2 gene were assessed for their peak patterns in each patient's blood and tissue DNA to analyze MSI and loss of heterozygosity (LOH). Results: No MSI was observed in any of the patient at BAT26 loci. Though BAT26 is reported to be quasi monomorphic, but interestingly it was found to be polymorphic in one patient. In D2S123 loci microsatellite alterations (MA) were observed in 50% of the OSCC patients, which comprised of both LOH and MSI. MA was observed to be significantly increased in moderately differentiated OSCC tumors. These MSI and LOH were independent of clinicopathological characteristics and mutation profile of hMSH2. Conclusion: Higher incidence of MSI at D2S123 in OSCC tumors could be indicative of diagnostic significance. However, this needs to be validated further in increased sample size and across different ethnic population.