High resolution genomic analses of oral cancer

High density Illumina 550K BeadChip arrays were used to identify copy number and copy neutral genomic aberrations in a panel of mortal and immortal PMOLs and OSCC cell lines (which included 11 mortal PMOLs, 7 immortal PMOLs, 3 mortal OSCCs and 17 immortal OSCCs).  Mortal PMOLs and OSCCs showed relatively few  changes. The changes in PMOLS and OSCCs were largely similar but there was a progressive increase in the frequency of the changes. In addition a small number of novel changes were identified in OSCCs that were absent in PMOLs.

The most common changes in immortal OSCCs were copy number losses involving chromosomal arms 9p (93%), 3p (93%) 8p (57%) and 13q (57%) and the highest frequency of copy number gains on chromosomal arms 3q (78%), 8q (85%), 9q (57%), 14q (57%) and 17q (57%). Copy number changes (deletions and amplifications) of loci encompassing known tumour suppressor genes or oncogenes and implicated in OSCC were identified. In addition, changes involving several other loci were also observed.

Several genes showing variable frequency of homozygous deletions (± homozygous deletions) were selected for further analysis. SSCP-HD analyses identified rare pathological mutations only in FAT1 and ARGBP2. Significant promoter methylation was demonstrated for genes ADAMTS9, CSMD1 and PDE4D both in immortal PMOLs and OSCCs and a panel of primary OSCCs. Quantitative transcript expression analysis showed decreased expression of CSMD1, ADAMTS9 in primary OSCCs. CSMD1 and ADAMTS9 showed reduced expression in a number of tumour types. These data support a tumour suppressive role for some of the genes analysed.