Germ Cell Proteins in Melanoma: Prognosis, Diagnosis, Treatment, and Theories on Expression

Abstract

Germ cell protein expression in melanoma has been shown to correlate with malignancy, severity of disease and to serve as an immunologic target for therapy. However, very little is known about the role that germ cell proteins play in cancer development. Unique germ cell pathways include those involved in immortalization, genetic evolution, and energy metabolism. There is an ever increasing recognition that within tumors there is a subpopulation of cells with stem-cell-like characteristics that play a role in driving tumorgenesis. Stem cell and germ cell biology is intertwined. Given the enormous potential and known expression of germ cell proteins in melanoma, it is possible that they represent a largely untapped resource that may play a fundamental role in tumor development and progression. The purpose of this paper is to provide an update on the current value of germ cell protein expression in melanoma diagnosis, prognosis, and therapy, as well as to review critical germ cell pathways and discuss the potential roles these pathways may play in malignant transformation.

Potential Role of Meiosis Proteins in Melanoma Chromosomal Instability

“…REC8 expression has been noted in melanoma [2] and we found it to be overexpressed in melanoma using western blot analysis (Figure 1) and immunofluorescence (Figure 2). REC8 has also been noted in irradiated lymphoma cells [22].…”

“…In fact, CIN is one of the most useful molecular markers to differentiate melanomas from benign nevi [1, 2]. Bastian et al found that 96.2% of melanomas demonstrated chromosomal aberrations while only 13.0% of benign nevi showed these same abnormalities, of which all were Spitz nevi with stable 11p duplications [1].…”

“…Cancer/testis antigens (CTAs) are a family of germ cell proteins expressed in a multitude of different histological tumor types [13, 14]. These proteins have been noted to have both diagnostic and prognostic value [2]. Studies have shown that expression of specific CTAs in melanoma can be used to predict tumor thickness, the presence of ulceration, and likelihood to undergo metastasis [15].…”

“…Studies have shown that expression of specific CTAs in melanoma can be used to predict tumor thickness, the presence of ulceration, and likelihood to undergo metastasis [15]. Melanomas have also been shown to express meiosis specific proteins including SCP1 (homologous chromosome pairing) [16], HORMAD1 (meiotic synapse regulation) [17], SPO11 (double stranded DNA breaks) [18], and REC8 (meiosis cohesion protein) [2]. We have also found three of these meiosis proteins, addition to a fourth not previously described, to be present in melanoma using western blot analysis (Figure 1) and immunofluorescence (Figure 2).…”

Meta‐analysis of expression of l(3)mbt tumor‐associated germline genes supports the model that a soma‐to‐germline transition is a hallmark of human cancers

“…Recent work from a range of organisms has revealed that tumors may acquire a more germline-like state. [4][5][6][7][8][9] Moreover, it has been demonstrated that the germline gene expression has the potential to be oncogenic in Drosophila melanogaster 4 and is associated with clinically more aggressive tumors in humans. 8 Janic et al recently demonstrated that l(3)mbt tumors in D. melanogaster ectopically expressed a broad range of germline genes, with up to a quarter of ectopically expressed genes being associated with a known germline function.…”