Germline mutations identified in melanoma-prone kindreds can impair the function of the p14ARF tumour suppressor

在澳大利亚，大约10%的人患黑色素瘤的风险很高，因为他们携带有缺陷的基因。这些易患黑色素瘤的个体中有许多携带一种突变，这种突变可以破坏两个基因p16INK4a和p14ARF。这些基因都通过不同的途径参与调节细胞的生长。p16INK4a在癌症发展中的作用已得到证实，该基因的许多功能正在深入研究中。相比之下，p14ARF在黑色素瘤进展中的作用尚未得到研究。我们将详细分析p14ARF缺陷是如何促进不受控制的细胞生长和癌症发展的。我们的研究将解剖p14ARF的功能，并确定p14ARF和p16INK4a是否协同维持正常的细胞生长。这项工作对我们了解黑色素瘤的发展至关重要，并将提供有关人类癌症生物学的临床有用信息。

Approximately 10% of people in Australia are at high risk of developing melanoma because they carry a faulty gene. Many of these melanoma-prone individuals carry a single mutation that can disrupt two genes, p16INK4a and p14ARF. These genes are both involved in regulating the growth of cells via different pathways. The role of p16INK4a in cancer development is well established and the many functions of this gene are under intense investigation. In contrast, the role of p14ARF in melanoma progression has not been studied. We will be analysing in detail how faulty p14ARF promotes uncontrolled cell growth and cancer development. Our research, will dissect the functions of p14ARF and determine whether p14ARF and p16INK4a co-operate in maintaining normal cell growth. This work is essential to our understanding of melanoma development and will provide clinically useful information regarding the biology of human cancer.