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CancerQuest > Introduction to Patient Information > Introduction to Cancer by Type > Introduction to Skin Cancer > Skin Cancer: Tumor Biology

Skin Cancer: Tumor Biology

 Genetic changes that occur in cancer cells include mutation of key regulatory genes, changes in protein products, and changes in the amount of product produced by genes (gene expression). As changes accumulate, cells become more abnormal and cancer may result. Details of genetic change associated with cancer can be found in the Mutation section. Some of the genetic elements that have been shown to be important in the development of skin cancer are discussed below:

MC1R Gene and α-melanocyte-stimulating hormone
The melanocortin receptor is responsible for binding alpha-melanocyte-stimulating hormone, the signal that initiates melanin production. Fair skinned individuals have polymorphisms which reduce the affinity of MC1R resulting in decreased MC1R:alpha-MSH binding. As a result, melanin production is reduced, increasing the individual's risk of developing melanoma. ⁽¹⁾

CDKN2A
CDKN2A refers to a region of DNA coding for two tumor suppressor proteins:
Ink4A and Arf. Both proteins play a key role in cell cycle regulation. Reduced activity of these proteins has severe consequences on the ability of cells to regulate cell division. Mutations in CDKN2A result in reduced function of the p53 and RB tumor suppressor pathways. ⁽²⁾

RAS Genes
RAS refers to a group of genes which are often mutated in cancer of many different types, melanoma included. The protein products are involved in transmitting signals through cells (also called "signal transduction") and are involved in numerous processes. Mutated RAS may increase malignant cell proliferation and reduce apoptosis. The pathways controlled by RAS have been found to be very frequently disrupted in melanoma cells.⁽²⁾

RAF Genes
The products of the three known RAF genes (RAF-1, ARAF and BRAF) function in the RAS pathway. The proteins are serine/threonine kinases and they function to transmit signals through the cell, influencing cell division. The BRAF gene product also seems to be involved in cell death (apoptosis). In one study, mutations in BRAF genes were observed in 66% of melanoma cell lines examined. ⁽²⁾⁽³⁾

Bcl-2
This gene encodes a protein that regulates apoptosis. Mutations which increase expression of Bcl-2 or enhance its function tend to reduce cell death and favor cancer development. ⁽²⁾

References for this page:

1. van der Velden P, Lodewijk S, Bergman W, et al. "Melanocortin-1 Receptor Variant R151C Modifies Melanoma Risk in Dutch Families with Melanoma." American Journal of Human Genetetics. 69:774779, 2001. [PUBMED]
2. Haluska FG, Tsao H, et al. "Genetic alterations in signaling pathways in melanoma." Clinical Cancer Research. 2006 Apr 1;12(7 Pt 2):2301s-2307s. [PUBMED]
3. Davies H, Bignell GR, et al. "Mutations of the BRAF gene in human cancer." Nature. 2002 Jun 27;417(6892):949-54. [PUBMED]