Microarray profiles of human basal cell carcinoma: insights into tumor growth and behavior.
OBJECTIVE
Basal cell carcinoma (BCC) is the most common human neoplasm. Much interest lies in determining the genetic basis of BCC to explain the unique locally invasive phenotype and infrequent metastatic behavior of these skin tumors.


OBJECTIVE
We sought to examine a gene expression profile for BCC to elucidate new molecules responsible for its unique growth characteristics.


METHODS
We analyzed gene expression patterns of 50 BCC tumors using spotted cDNA microarrays of 1718 characterized human genes related to cancer and immunity. This is the largest and most comprehensive gene expression study ever performed for BCC. Nodular and sclerosing histological subtypes of BCC were examined and compared to normal control skin. After statistical filtering, 374 significantly dysregulated genes were sorted by hierarchical clustering to determine trends of gene expression and similarities between patient gene expression profiles.


RESULTS
A total of 165 upregulated genes and 115 downregulated genes were identified. These covered a range of categories, including extracellular matrix, cell junctions, motility, metastasis, oncogenes, tumor suppressors, DNA repair, cell cycle, immune regulation and angiogenesis. Clusters of genes were either commonly dysregulated across the 50 patient sample, or selectively affected in subsets of tumors. Histological subtypes were not distinguishable by hierarchical clustering. Many of the genes elucidated, including collagen type IV subunits and other novel candidates, possess functions related to extracellular matrix remodeling and metastasis.


CONCLUSIONS
These results suggest a gene profile which may explain the invasive growth yet rarely metastatic behavior of BCC. The genes identified may also be potential targets for therapeutics aimed at further controlling invasiveness and local destruction of BCC.
Howell
Brandon G
BG
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0900, USA.
Solish
Nowell
N
Lu
Chao
C
Watanabe
Hideaki
H
Mamelak
Adam J
AJ
Freed
Irwin
I
Wang
Binghe
B
Sauder
Daniel N
DN
D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology*; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics; D003094:Collagen / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D007633:Keratins / Q000235:genetics / Q000502:physiology; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D000075746:Zinc Finger Protein Gli2
D051242:Caveolin 1; D022461:Caveolins; D004268:DNA-Binding Proteins; C082593:GLI2 protein, human; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D000075746:Zinc Finger Protein Gli2; D007633:Keratins; D003094:Collagen; D010749:Phosphoprotein Phosphatases