Amplification of the PPFIA1 gene region on 11q13 in oral squamous cell carcinomas (OSCC)

INTRODUCTION: Analyzing chromosomal amplifications delivers valuable information for identification of oncogenes. For carcinomas of the oral cavity only few genes have been identified in amplified regions. The aim of this study was to search genes in amplified regions as possible biomarkers and targets for novel therapies.

MATERIAL AND METHODS: DNA from 10 carcinomas of the floor of the oral cavity was examined using a 500K Array GeneChip (Affymetrix 6.0) to detect chromosomal losses, gains or amplifications. Suspicious alterations were validated on tissue microarrays using fluorescence in situ hybridization (FISH) with respective probes.

RESULTS: FISH-validation on tissue arrays confirmed PPFIA1 amplifications as one of the most frequent events (32.6%). High (10-20 signals) and low (<10 signals) amplification of PPFIA1 was found in 10.9% (5/46) and 21.7% (10/46) tumours, respectively. Fine mapping with overlapping FISH probes showed co-amplification of PPFIA1 and the Cyclin D1 gene which are approximately 600 kb apart from each other, likely in the same amplicon.

DISCUSSION: PPFIA1 was frequently co-amplified with the Cyclin D1 gene in oral carcinomas and could present a biomarker as well as a novel target for specific gene therapy. Further studies are necessary to investigate the role of PPFIA1 in development and pathogenesis of oral carcinomas.