Genomewide single nucleotide polymorphism microarray mapping in basal cell carcinomas unveils uniparental disomy as a key somatic event

Muy-Teck Teh, Diana Blaydon, Tracy Chaplin, Nicola J. Foot, Spyros Skoulakis, Manoj Raghavan, Catherine A. Harwood, Charlotte M. Proby, Michael P. Philpott, Bryan D. Young, David P. Kelsell

    Research output: Contribution to journalArticlepeer-review

    128 Citations (Scopus)


    Basal cell carcinoma is the most common human cancer with increasing incidence reported worldwide. Despite the aberrant signaling role of the Hedgehog pathway, little is known about the genetic mechanisms underlying basal cell carcinomas. Towards a better understanding of global genetic events, we have employed the Affymetrix Mapping 10K single nucleotide polymorphism (SNP) microarray technique for “fingerprinting” genomewide allelic imbalance in 14 basal cell carcinoma–blood pair samples. This rapid high-resolution SNP genotyping technique has revealed a somatic recombination event–uniparental disomy, leading to a loss of heterozygosity (LOH), as a key alternative genetic mechanism to allelic imbalances in basal cell carcinomas. A highly conserved LOH region at 9q21-q31 was found in 13 of 14 (93%) basal cell carcinomas. Further statistical and fluorescence in situ hybridization analyses confirmed that the 9q LOH was a result of uniparental disomy in 5 of 13 (38%) basal cell carcinomas. De novo mutations in the Patched 1 gene (PTCH) were found in 9 of 13 (69%) basal cell carcinomas with 9q LOH. A second important locus, containing LOH at 6q23-q27 was found in 5 of 14 (36%) basal cell carcinomas, suggesting that the presence of an additional putative tumor suppressor gene may be contributing to basal cell carcinoma development. This study shows that the rate of 9q LOH in basal cell carcinomas has been previously underestimated. Furthermore, we provide the first evidence that uniparental disomy due to somatic recombination constitutes one of the mechanisms of LOH in basal cell carcinoma tumorigenesis.
    Original languageEnglish
    Pages (from-to)8597-8603
    Number of pages7
    JournalCancer Research
    Issue number19
    Publication statusPublished - Oct 2005


    • Basal cell carcinoma
    • Loss of heterozygosity
    • SNP microarray
    • Allelic imbalance
    • Uniparental disomy


    Dive into the research topics of 'Genomewide single nucleotide polymorphism microarray mapping in basal cell carcinomas unveils uniparental disomy as a key somatic event'. Together they form a unique fingerprint.

    Cite this