€ RREB1: The protein encoded by RREB1 binds specific sequences, RAS-response elements (RRE), and regulates expression of RRE containing genes. RREB1 can both up- and down-regulate target gene expression. This gene is found on the short arm of chromosome 6, in a region commonly amplified in multiple cancers, including melanoma. 6p amplification is the most common chromosomal abnormality seen in melanoma. Furthermore, amplification has been associated with lower survival compared to those without 6p amplification (Cancer Biomarkers (2016) 16(4): 575-597).
€ MYB: MYB is a proto-oncogene that transcriptionally regulates gene expression. This protein plays an essential role in hematopoiesis through control of proliferation and differentiation of hematopoietic progenitor cells.
€ c-MYC: This transcriptional regulator is able to bind DNA in both specific and non-specific manners to modulate transcription of genes associated with cell cycle progression, apoptosis, and cellular transformation. Amplification of c-MYC is a known occurrence in metastatic melanoma (Journal of Molecular Medicine (2017) 95(1): 53-67).
€ CDKN2A: CDKN2A has multiple transcripts that result in distinct proteins after translation. One product leads to inhibition of CDK4 while another is known to sequester and inhibit MDM2 activity. Together, CDKN2A isoforms regulate G1 cell cycle control. This gene is mutated or deleted in multiple cancers, including melanoma. Germline mutations are reported in 20-40% familial melanoma cases while these mutations are reported in 0.2-2% of sporadic melanomas. Co-occurrence of NRAS or BRAF mutations are estimated at 16% and 37%, respectively (Journal of American Academy of Dermatology (2015) 72(3): 496-507). Furthermore, homo- or heterozygous loss of CDKN2A has been reported in 56% of primary invasive melanomas. Current research is focused on determine the efficacy of CDK4 inhibition for treating melanomas with CDKN2A aberrations (Pigment Cell and Melanoma (2014) 27(4): 590-600).
€ CCND1: CCND1 encodes cyclin D1, a regulator of CDK4/CDK6. CCND1 complexes with CDK4 to phosphorylate and inhibit RB1 family members to regulate G1/S cell cycle transition. A recent study reported loss of CCND1 occurred at a frequency of 38.7% in melanoma (Clinical Cancer Research (2016) 22(2): 374-382).