title: Investigation of the molecular profile of basal cell carcinoma using whole genome microarrays.
abstract: BACKGROUND
  Skin cancer accounts for 1/3 of all newly diagnosed cancer. Although seldom fatal, basal cell carcinoma (BCC) is associated with severe disfigurement and morbidity. BCC has a unique interest for researchers, as although it is often locally invasive, it rarely metastasises. This paper, reporting the first whole genome expression microarray analysis of skin cancer, aimed to investigate the molecular profile of BCC in comparison to non-cancerous skin biopsies. RNA from BCC and normal skin specimens was analysed using Affymetrix whole genome microarrays. A Welch t-test was applied to data normalised using dCHIP to identify significant differentially-expressed genes between BCC and normal specimens. Principal component analysis and support vector machine analysis were performed on resulting genelists, Genmapp was used to identify pathways affected, and GOstat aided identification of areas of gene ontology more highly represented on these lists than would be expected by chance.
  
  
  RESULTS
  Following normalisation, specimens clustered into groups of BCC specimens and of normal skin specimens. Of the 54,675 gene transcripts/variants analysed, 3,921 were differentially expressed between BCC and normal skin specimens. Of these, 2,108 were significantly up-regulated and 1,813 were statistically significantly down-regulated in BCCs.
  
  
  CONCLUSIONS
  Functional gene sets differentially expressed include those involved in transcription, proliferation, cell motility, apoptosis and metabolism. As expected, members of the Wnt and hedgehog pathways were found to be significantly different between BCC and normal specimens, as were many previously undescribed changes in gene expression between normal and BCC specimens, including basonuclin2 and mrp9. Quantitative-PCR analysis confirmed our microarray results, identifying novel potential biomarkers for BCC.
authors.affiliation: National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland. Lorraine.odriscoll@dcu.ie
authors.forename: Lorraine
authors.initials: L
authors.lastname: O'Driscoll
authors.forename: Jason
authors.initials: J
authors.lastname: McMorrow
authors.forename: Padraig
authors.initials: P
authors.lastname: Doolan
authors.forename: Eadaoin
authors.initials: E
authors.lastname: McKiernan
authors.forename: Jai Prakash
authors.initials: JP
authors.lastname: Mehta
authors.forename: Eoin
authors.initials: E
authors.lastname: Ryan
authors.forename: Patrick
authors.initials: P
authors.lastname: Gammell
authors.forename: Helena
authors.initials: H
authors.lastname: Joyce
authors.forename: Norma
authors.initials: N
authors.lastname: O'Donovan
authors.forename: Nicholas
authors.initials: N
authors.lastname: Walsh
authors.forename: Martin
authors.initials: M
authors.lastname: Clynes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000592:standards; D016133:Polymerase Chain Reaction / Q000379:methods; D015203:Reproducibility of Results; D012867:Skin / Q000378:metabolism*; D013223:Statistics as Topic