Molecular classification of cutaneous malignant melanoma by gene expression profiling

Abstract

The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm. Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities. Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas. Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.

Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling

“…Genome-wide analysis of gene expression using microarray technology is proving an important aid in the molecular diagnosis and classification of human malignancies including leukaemias and lymphomas (Golub et al, 1999;Alizadeh et al, 2000), breast cancer (Perou et al, 2000;Sorlie et al, 2001) and melanoma (Bittner et al, 2000). In the current study, we have used a cDNA microarray technique to obtain expression profiles for three diagnostic categories of adult soft tissue sarcomas: synovial sarcomas, leiomyosarcomas and MFHs.…”

Genomic profiling of malignant melanoma using tiling-resolution arrayCGH

“…powerful tools in this respect, for example, revealing gene sets that allow discrimination of vertical and radial growing CMM and that can be used for class discovery (Bittner et al, 2000;Haqq et al, 2005). Moreover, arrayCGH unraveled genomic aberrations specific for chronic sun-induced melanomas, and indicated that alteration in the CDKN2A and PI3K pathways are independent but complementary events in melanoma pathogenesis (Curtin et al, 2005).…”

Ubiquitous mitochondrial creatine kinase downregulated in oral squamous cell carcinoma

“…Gene expression profiles using cDNA microarrays have been used to derive a useful molecular-based classification for the diagnosis, treatment, and prevention of several cancers (Alizadeh et al, 2000;Bittner et al, 2000). However, biologic systems comprise protein components resulting from transcriptional and post-transcriptional control, post-translational modifications, and protein shifts among different cellular compartments.…”