A gene expression signature of invasive potential in metastatic melanoma cells.
BACKGROUND
We are investigating the molecular basis of melanoma by defining genomic characteristics that correlate with tumour phenotype in a novel panel of metastatic melanoma cell lines. The aim of this study is to identify new prognostic markers and therapeutic targets that might aid clinical cancer diagnosis and management.


RESULTS
Global transcript profiling identified a signature featuring decreased expression of developmental and lineage specification genes including MITF, EDNRB, DCT, and TYR, and increased expression of genes involved in interaction with the extracellular environment, such as PLAUR, VCAN, and HIF1a. Migration assays showed that the gene signature correlated with the invasive potential of the cell lines, and external validation by using publicly available data indicated that tumours with the invasive gene signature were less melanocytic and may be more aggressive. The invasion signature could be detected in both primary and metastatic tumours suggesting that gene expression conferring increased invasive potential in melanoma may occur independently of tumour stage.


CONCLUSIONS
Our data supports the hypothesis that differential developmental gene expression may drive invasive potential in metastatic melanoma, and that melanoma heterogeneity may be explained by the differing capacity of melanoma cells to both withstand decreased expression of lineage specification genes and to respond to the tumour microenvironment. The invasion signature may provide new possibilities for predicting which primary tumours are more likely to metastasize, and which metastatic tumours might show a more aggressive clinical course.
Jeffs
Aaron R
AR
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand. aaron.jeffs@otago.ac.nz
Glover
Amy C
AC
Slobbe
Lynn J
LJ
Wang
Li
L
He
Shujie
S
Hazlett
Jody A
JA
Awasthi
Anshul
A
Woolley
Adele G
AG
Marshall
Elaine S
ES
Joseph
Wayne R
WR
Print
Cristin G
CG
Baguley
Bruce C
BC
Eccles
Michael R
MR
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008957:Models, Genetic; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*
D009363:Neoplasm Proteins; D012333:RNA, Messenger