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.

Analysis of protein expression profile of oral squamous cell carcinoma by MALDI-TOF-MS.

In this study, two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF-MS) technology was used to examine differentially expressed proteins in oral squamous cell carcinoma (OSCC) tissues from Norway (n=15) and the UK (n=45). Twenty-nine proteins were found to be significantly overexpressed in the OSCCs examined compared to the normal controls. Identified proteins included, family of annexin proteins that play important roles in signal transduction pathways and regulation of cellular growth, keratin-1, heat-shock proteins (HSP), squamous cell carcinoma antigen (SCC-Ag), cytoskeleton proteins, and proteins involved in mitochondrial and intracellular signalling pathways. The expression of four selected proteins (annexin II and V, HSP-27, and SCC-Ag) was verified using western blot analysis of 76 fresh tissue biopsy specimens in total, from Norway (n=53) and the UK (n=23). Proteomic analysis of OSCCs examined here demonstrated involvement of several proteins that might function as potential biomarkers and molecular targets for early cancer diagnostics, and may contribute to a novel approach to therapeutics and for predicting prognosis of OSCC.

Gene expression analysis by cDNA microarray in oral cancers from two Western populations.

BACKGROUND: In this work, gene expression profile was examined in 19 cases of oral cancer (OC) obtained from patients from Sweden (n=8) and UK (n=11) and the findings were tested for correlation to patient's clinicopathological data. MATERIALS AND METHODS: Following total RNA extraction, cDNA synthesis, labeling with fluorescent dyes and hybridization to the 21 k human oligonucleotide microarrays, slides were scanned and images were subjected to Genepix and J-Express analysis. Results for selected genes were validated by quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR). RESULTS: 42 genes were identified as being differentially expressed. These included 39 genes of known functions (such as fatty acid synthase (FASN), 5' nucleotidase, ecto (NT5E), high mobility group AT-hook (HMGA1), and v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS)) and 3 novel genes; 26 (67%) of the 39 genes with known functions were previously reported in oral/head and neck tumors examined from other populations. Hierarchical clustering of the samples using the 42 genes demonstrated that samples mainly clustered in the same population. CONCLUSION: These results illustrate that microarrays can be used to identify distinct patterns of gene expression in different populations, but with no direct association to clinicopathological parameters. The fact that 67% of the 39 genes with known functions found in this work were previously reported in oral/head and neck tumors from other populations provides clear evidence that development of these tumors follows the same biological pathways irrespective of the source of the samples used.