Ghosh Papia, Chin Lynda
Dana-Farber Cancer Institute, Department of Medical Oncology, 44 Binney Street, Boston, MA 02215, USA, Tel.: +1 617 258 8614, ,
Expert Rev Dermatol. 2009 Apr 1;4(2):131. doi: 10.1586/edm.09.2.
The rapidly increasing incidence of melanoma, coupled with its highly aggressive metastatic nature, is of urgent concern. In order to design rational therapies, it is of critical importance to identify the genetic determinants that drive melanoma formation and progression. To date, signaling cascades emanating from the EGF receptor, c-MET and other receptors are known to be altered in melanoma. Important mutations in signaling molecules, such as BRAF and N-RAS, have been identified. In this review, some of the major genetic alterations and signaling pathways involved in melanoma will be discussed. Given the great deal of genetic heterogeneity observed in melanoma, it is likely that many more genetic determinants exist. Through the use of powerful genomic technologies, it is now possible to identify these additional genetic alterations in melanoma. A critical step in this analysis will be culling bystanders from functionally important drivers, as this will highlight genetic elements that will be promising therapeutic targets. Such technologies and the important points to consider in understanding the genetics of melanoma will be reviewed.
黑色素瘤发病率的迅速上升，加上其高度侵袭性的转移特性，令人迫切担忧。为了设计合理的治疗方案，识别驱动黑色素瘤形成和进展的遗传决定因素至关重要。迄今为止，已知源自表皮生长因子受体、c-MET和其他受体的信号级联在黑色素瘤中发生改变。已经确定了信号分子中的重要突变，如BRAF和N-RAS。在本综述中，将讨论黑色素瘤中一些主要的基因改变和信号通路。鉴于在黑色素瘤中观察到大量的基因异质性，可能存在更多的遗传决定因素。通过使用强大的基因组技术，现在有可能识别黑色素瘤中的这些额外基因改变。该分析中的关键一步将是从功能重要的驱动因素中剔除旁观者，因为这将突出那些有望成为治疗靶点的遗传元件。将对这类技术以及在理解黑色素瘤遗传学中需要考虑的要点进行综述。
