Profiling of chromosomal changes in potentially malignant and malignant oral mucosal lesions from South and South-East Asia using array-comparative genomic hybridization.

Background/aim: Using array-CGH, the present study aimed to explore genome-wide profiles of chromosomal aberrations in samples of oral cancer (OC), oral submucous fibrosis (OSF) and their corresponding normal oral mucosa from Indian (n=18) and OC from Sri Lankan (n=12) patients with history of BQ use, and correlate the findings to other clinicopathological parameters. A second aim was to verify the results from the array-CGH by selecting a candidate gene, S100A14, and examine its expression and genetic polymorphisms by immunohistochemistry (IHC) and restriction fragment length polymorphism (RFLP) using samples from both populations and from multi-national archival DNA and paraffin-embedded samples of OC.

Results: In OC and OSF samples, 80 chromosomal regions (harboring 349 genes) were found as deleted or amplified. Out of the 349 genes, 34 (including several S100 gene family members) were found to be deleted and 30 (containing NOTCH4, TP53 and ERBB2) were found as amplified in OSF and OC cases. 285 genes (including TP53, ERBB2 and BRCA1) were found either as deleted in one population or amplified in the other. Few chromosomal alterations were found to be exclusive to either OC or OSF samples alone. IHC demonstrated down-regulation and transfer of S100A14 protein expression from membrane to cytoplasmic. RFLP showed differential distribution between Asian samples compared to African and Western samples at 461 G>A SNP.

Conclusion: The present study provides findings on chromosomal aberrations likely to be involved in pathogenesis of OC and OSF. Findings of chromosomal changes harboring genes previously found in OC examined from Western, African and Asian populations demonstrate the importance of these changes in development of OC, and the existence of common gene-specific amplifications/deletions, regardless of source of samples or attributed risk factors. We report a down-regulation of S100A14 expression to be a significant marker in association with loss of 1q21 in 70% of OC samples.