Malignant melanoma originates from the pigment-producing melanocytes in the epidermal basal layer, and is considered to develop in a multi-step process. By using a systems level approach to analyze the melanoma proteome with respect to clinical outcome based on genome-wide transcriptomics, 205 genes were found to be associated with prognostic outcome.

As part of the release of the Pathology Atlas, the Human Protein Atlas News will present brief summaries of several cancers included in the atlas, and highlight genes with prognostic association in the different cancer forms. Click here if you missed the latest blog post about pancreatic cancer.

Malignant melanoma is the leading cause of skin-related death in Caucasians, but rare in populations with darker pigmented skin color. Malignant melanoma is thought to develop in a multi-step process, and originates from the pigment-producing melanocytes in the epidermal basal layer. The incidence of melanoma has increased dramatically during the last decades, with an almost four-fold increase in the Nordic countries in the time period 1964-2003. Short intermittent exposure with sunburns appears to be the main risk factor, but skin type and hereditary risk factors are also important. Other significant risk factors include the number of melanocytic nevi and the number of dysplastic melanocytic nevi.

The analysis of prognostic genes in melanoma was based on publically available gene expression data and clinical metadata from the Cancer Genome Atlas (TCGA) consisting of 102 patients with different stages of melanoma. According to the analysis, 205 genes were associated with prognostic outcome, out of which 163 genes were associated with unfavourable prognosis and 42 genes with favourable prognosis.

The MCM6 gene encodes a component of the highly conserved mini-chromosome maintenance (MCM) proteins. MCM proteins are essential for initiation of chromatin replication. The MCM6 gene is shown to be associated with unfavourable prognosis in melanoma. Immunohistochemical staining of MCM6 shows a differential nuclear expression pattern in melanoma patient samples (Figure 1).

The WD repeat domain phosphoinositide-interacting protein 1, or WIPI1, plays an important role in mitophagy, which is the degradation of mitochondria via autophagy. WIPI1 is also implicated in starvation- and calcium-mediated autophagy. The WIPI1 gene is shown to be associated with favourable prognosis in melanoma. Immunohistochemical staining of WIPI1 shows a differential expression pattern restricted to the cytoplasm in melanoma patient samples (Figure 2).

Interested to know more about the Pathology Atlas? Read a summary previously posted on the blog here. Also, do not miss the related research article published in Science.

Explore the Melanoma Proteome and search for your gene of interest in our Pathology Atlas!

References and links

Histology dictionary - Melanoma

Borbala Katona