Genome-Wide Fingerprinting in Basal Cell Carcinomas
Objectives: Basal cell carcinoma (BCC) occurs primarily in the head and neck regions and is the commonest human cancer with over 8 million cases reported worldwide in 2002. Despite the well characterised role of the Hedgehog pathway, little is known about the genetic mechanisms underlying BCCs.
Methods: Towards a better understanding of global genetic events, we have employed the Affymetrix Mapping 10K single-nucleotide polymorphism (SNP) microarray technique for fingerprinting genome-wide allelic imbalance in 14 BCC-blood pair samples.
Results: This rapid, highly reproducible and high resolution SNP genotyping technique has revealed a somatic recombination event -- uniparental disomy (UPD), leading to a loss of heterozygosity (LOH), as a key alternative genetic mechanism to allelic imbalances in BCCs. A highly conserved region of LOH at 9q21-q31 was found in 13/14 (93%) BCCs. Further statistical and FISH analyses confirmed that the LOH at 9q was a result of UPD in 5/13 (38%) BCCs. De novo mutations in the Patched 1 gene (PTCH) were found in 9/13 (69%) BCCs with 9q LOH. A second important locus, containing LOH at 6q23-q27 was found in 5/14 (36%) BCCs, suggesting the presence of an additional putative tumour suppressor gene may be contributing to BCC development.
Conclusions: This study demonstrates that the rate of 9q LOH in BCCs has been previously underestimated. Furthermore, we provide the first evidence that UPD due to somatic recombination constitutes one of the mechanisms of LOH in BCC tumourigenesis.
Division: Continental European and Scandinavian Divisions Meeting
Meeting:2005 Continental European and Scandinavian Divisions Meeting (Amsterdam, Netherlands) Location: Amsterdam, Netherlands
Year: 2005 Final Presentation ID:559 Abstract Category|Abstract Category(s):Scientific Program
Authors
Teh, Muy-teck
( Queen Mary University of London, London, N/A, United Kingdom
)
Young, Bryan D.
( Queen Mary University of London, London, N/A, United Kingdom
)
Kelsell, David P.
( Queen Mary University of London, London, N/A, United Kingdom
)
Blaydon, Diana
( Queen Mary University of London, London, N/A, United Kingdom
)
Chaplin, Tracy
( Queen Mary University of London, London, N/A, United Kingdom
)
Foot, Nicola J.
( Queen Mary University of London, London, N/A, United Kingdom
)
Skoulakis, Spyros
( Queen Mary University of London, London, N/A, United Kingdom
)
Raghavan, Manoj
( Queen Mary University of London, London, N/A, United Kingdom
)
Harwood, Catherine A.
( Queen Mary University of London, London, N/A, United Kingdom
)
Proby, Charlotte M.
( Queen Mary University of London, London, N/A, United Kingdom
)
Philpott, Michael P.
( Queen Mary University of London, London, N/A, United Kingdom
)