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Essay: Cutaneous melanoma

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  • Published: 2 May 2018*
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  • Words: 592 (approx)
  • Number of pages: 3 (approx)

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Cutaneous melanoma represents the fastest growing cancer by incidence in the United States. Our group set out to contribute to the search for better biomarkers in order to improve current diagnostic capabilities towards melanoma. Our groups in silico investigations began by identifying genes with the strongest co-expression to tyrosinase (TYR), a well-known marker in melanoma samples. C10ORF90 demonstrated the best co-expression to TYR in melanoma cell lines. Several additional computer-based investigations were used to further characterize C10ORF90, including: The Human Protein Atlas (HPA), Gene Expression Omnibus (GEO), String-db.org (STRING), Cluster 3.0, and BioGPS.

We were able to demonstrate high expression of C10ORF90 in melanoma cell lines. Furthermore, through String and Cluster analyses, we were able to show that the expression of C10ORF90 correlates to a number of genes related to tumorigenesis, including: p53, PTEN, MDM2, SILV, TYR, DOCK1, BRCA1.

In conclusion, our group was able to further characterize C10ORF90, with respect to its potential centrosomal interactions as well as its involvement in melanoma. This, in addition to the numerous novel protein associations that were found, should warrant further investigation of C10ORF90 as a potential biomarker or drug-target in melanoma.

INTRODUCTION

Cutaneous melanoma has the fastest growing incidence of any malignancy in the United States, with an annual percentage increase of 2.8% in the past two decades (SEER, 2017). As such, improving the diagnostic capabilities to achieve earlier identification of metastatic potential is of great importance to attenuate overall mortality and morbidity. Dermatopathologists currently differentiate melanoma based on histological and immunohistological exam (Carli, 2004). Present research focuses on providing a valuable adjunct for better identification and differentiation of melanoma (Tsao, 2012). Alexandrescu and associates evaluated the performance of specific gene expression markers and showed their potential utility in improving melanoma diagnosis (Alexandrescu, 2010). Silver locus protein homolog (SILV) expression was applicable for the diagnosis of both unequivocal and suspicious cases, the latter proving to be a more difficult challenge for expert pathologists. It was suggested that a numerical probability score of malignancy, based on a quantitative real-time polymerase chain reaction assay, should be utilized as a supporting factor in diagnosis (Alexandrescu, 2010). Despite these findings, there is still a need for more specific markers of malignant melanoma, especially in regard to identifying early neoplastic change.

With hopes of contributing to the search for better biomarkers, and proteins potentially involved in the carcinogenesis of melanoma, we began by investigating minimally characterized genes with a high degree of Tyrosinase (TYR) co-expression, a well-established marker in melanoma samples. One of the genes demonstrating the strongest co-expression was C10ORF90. At the time of investigation, few papers were found annotating C10ORF90; one of which suggested a possible centrosomal function (Knorz, 2010). Considering the pervasiveness of centrosomal abnormalities in cancer (Chan, 2011), a possible oncogenic process involving the centrosome was hypothesized.

The role of the centrosome in the progression of melanoma has gone largely unexplored, but it is well established that centrosome abnormalities are an important cause of chromosome instability (Lingle, 2002); which both frequently co-occur in carcinoma in situ (Pihan 1998). As such, centrosomal abnormalities appear to occur early in the course of most cancers; rather than a result of later effect (Pihan 2003). This supports the possibility that C10ORF90 may have some utility in identifying primary neoplastic change in melanocytes with further characterization. Accordingly, we hope to further describe this gene, especially in regard to its possible role in the centrosome and in the development of melanoma. The following sections will describe C10ORF90 in detail with respect to the current body of knowledge and our in silico findings.

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