C64
Single nucleotide polymorphism microarray analysis defines a specific genetic fingerprint for well-differentiated cutaneous squamous cell carcinomas
Karin Purdie1, Catherine Harwood1, Abha Gulati1, Tracy Chaplin2, Sally Lambert1, Rino Cerio1, Gavin Kelly3, Jean-Baptiste Cazier3, Bryan Young2, Irene Leigh4, Charlotte Proby4
1Institute of Cell and Molecular Science, Queen Mary, University of London, London, UK, 2Institute of Cancer, Queen Mary, University of London, London, UK, 3Cancer Research UK London Research Institute, London, UK, 4Ninewells Hospital and Medical School, Dundee, UK
Background
Cutaneous squamous cell carcinomas (cSCC) are the second most frequent cancers in fair-skinned populations yet, because of their genetic heterogeneity, the key molecular events in cSCC tumorigenesis remain poorly defined.
Method
We have employed single nucleotide polymorphism (SNP) microarray analysis to examine genome-wide allelic imbalance in 60 cSCC using paired non-tumour samples.
Results
The most frequent recurrent aberrations were loss of heterozygosity (LOH) at 3p and 9p, observed in 39 (65%) and 45 (75%) tumours respectively. Microdeletions at 9p23 within the protein tyrosine phosphatase receptor type D (PTPRD) locus were identified in a total of 9 (15%) samples, supporting a tumour suppressor role for PTPRD in cSCC. In addition, microdeletions at 3p14.2 were detected in 3 (5%) cSCC, implicating FHIT as a possible target for inactivation. Statistical analysis revealed that well-differentiated cSCC demonstrated significantly fewer aberrations than moderately and poorly differentiated cSCC; yet, despite a lower rate of allelic imbalance, some specific aberrations were observed equally frequently in both groups. No correlation was established between the frequency of chromosomal aberrations and immune or human papillomavirus status.
Conclusion
Our data suggest that well differentiated tumours are a genetically distinct subpopulation of cSCC. Furthermore, our findings demonstrate the effectiveness of genome-wide SNP microarray analysis as a means of unravelling the genetic complexity of cSCC.
