The Impact of Genomics in Understanding Human Melanoma Progression and Metastasis

Ren, Shengxiang; Liu, Suhu; Howell, Paul; Xi, Yaguang; Enkemann, Steven A.; Ju, Jingfang; Riker, Adam I.

doi:10.1177/107327480801500303

Cited by 24 publications

(17 citation statements)

References 67 publications

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“…This loss of cell-stroma cross-talk is a well-known behavior of melanoma cells that acquired an increased migratory potential in an epithelial-mesenchymal transition. These findings were concordant with a previous ontological analysis that identified reduced expression or loss of genes involved in keratinocyte differentiation, epidermal development, cell adhesion, and cell-cell signaling in metastatic samples [10,55]. …”

Section: Discussionsupporting

confidence: 91%

“…Although many differentially expressed genes have been found, there is still no generally accepted histopathological or molecular marker defining disease subsets with clinically different outcomes [11,15,16,54,55]. This frustrating situation reflects the complexity of working with melanoma samples and the difficulty of comparing data generated from different array platforms using distinct statistical analysis and diverse cohorts [9].…”

Section: Discussionmentioning

confidence: 99%

“…Some of these genes had already been described in earlier studies as being down-regulated during melanoma progression: COL17A1 [15,18], DSC3 [15,18], KLK7 [10,15], SLPI and KLK8 [18], or over-expressed, e.g. CCL20 [55], THBS1 [55] and THBS4 [15]. However, other genes were here described for the first time as differentially expressed in melanoma tumors, such as COL4A1, FBN1, LAMA3, LAMA4, C1QR1, CTGF, VWF, CTGF, PLAU , CYR61 , and EMP1 .…”

Section: Discussionmentioning

confidence: 99%

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Gene network analyses point to the importance of human tissue kallikreins in melanoma progression

et al. 2011

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BackgroundA wide variety of high-throughput microarray platforms have been used to identify molecular targets associated with biological and clinical tumor phenotypes by comparing samples representing distinct pathological states.MethodsThe gene expression profiles of human cutaneous melanomas were determined by cDNA microarray analysis. Next, a robust analysis to determine functional classifications and make predictions based on data-oriented hypotheses was performed. Relevant networks that may be implicated in melanoma progression were also considered.ResultsIn this study we aimed to analyze coordinated gene expression changes to find molecular pathways involved in melanoma progression. To achieve this goal, ontologically-linked modules with coordinated expression changes in melanoma samples were identified. With this approach, we detected several gene networks related to different modules that were induced or repressed during melanoma progression. Among them we observed high coordinated expression levels of genes involved in a) cell communication (KRT4, VWF and COMP); b) epidermal development (KLK7, LAMA3 and EVPL); and c) functionally related to kallikreins (EVPL, KLK6, KLK7, KLK8, SERPINB13, SERPING1 and SLPI). Our data also indicated that hKLK7 protein expression was significantly associated with good prognosis and survival.ConclusionsOur findings, derived from a different type of analysis of microarray data, highlight the importance of analyzing coordinated gene expression to find molecular pathways involved in melanoma progression.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Gene network analyses point to the importance of human tissue kallikreins in melanoma progression

et al. 2011

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“…Gene expression profiling of breast tumours has resulted in sub-classification of cancers previously thought to be homogenous [10], allowing prediction of those most likely to benefit from chemotherapy [11] and overall survival [12]. Gene expression profiling has generated a number of insights into the molecular basis of melanoma over the last decade ([13]-[16]; reviewed in [17]), but this accumulation of knowledge has yet to provide clinical benefit in terms of improved patient treatment options or survival.…”

Section: Introductionmentioning

confidence: 99%

A Gene Expression Signature of Invasive Potential in Metastatic Melanoma Cells

et al. 2009

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BackgroundWe 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.Principal FindingsGlobal 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.ConclusionsOur 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.

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“…It is significant that 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 [Jeffs et al, 2009]. The impact of genomics on understanding human melanoma progression and metastasis was summarised by Ren et al [2008]. Several groups have found distinct differences in gene expression patterns along the spectrum of melanoma tumour progression, with many showing distinct sets of over-and underexpressed genes that have been validated as having distinct, key roles in melanoma progression.…”

Section: Gene Expression Profiling Of Melanomamentioning

confidence: 99%