Malignant Progression in Human Melanoma

大约一半的人类黑色素瘤起源于称为黑素细胞痣的前体细胞增殖。然而，大多数黑素细胞痣不会发生恶性转化，而是在一生中保持稳定或消失。为了了解黑素细胞转化的决定因素，特别是当它们适用于从黑素细胞痣前体病变发展为原发性人类黑色素瘤时，我们正在计划一项基于患者的研究，有两个目标。一种是更精确地定义早期原发性黑色素瘤的临床特征，使用皮肤发光显微镜或皮肤镜检查来观察与病变组织病理学相关的特定结构。二是对临床良性黑素细胞痣中的黑素细胞进行取样和永生化，以研究这些细胞中的信号通路和基因表达，从而进一步了解黑素细胞转化过程中常见的第一步。这项研究的一个潜在好处是，早期原发性黑素瘤的临床知识，加上使成人黑素细胞永生的技术的发展，可能使后续研究有可能从这些早期恶性病变中获得和扩增细胞，以了解这一阶段的恶性转化。这一点尤其重要，因为目前使用的大多数人类黑色素瘤细胞系要么来自晚期原发肿瘤，要么来自转移瘤，并且很少有与之相关的详细临床注释。

Approximately half of human melanomas originate from precursor melanocytic proliferations termed melanocytic nevi. However, most melanocytic nevi do not undergo malignant transformation, but rather remain stable throughout life or disappear. To understand the determinants of melanocyte transformation, especially as they apply to the development of primary human melanoma from melanocytic nevus precursor lesions, we are planning a patient-based study with two goals. One is to define the clinical characteristics of early primary melanomas with greater precision, using skin epiluminescent microscopy, or dermascopy, to visualize specific structures that can be correlated with lesional histopathology. The other is to sample and immortalize melanocytes from clinically benign melanocytic nevi, in order to study signalling pathways and gene expression in these cells to gain more insight into a common first step in the process of melanocyte transformation. One potential benefit of this study is that the clinical knowledge gained about early primary melanomas, combined with the development of techniques to immortalize adult human melanocytes, may make it possible in a subsequent study to obtain and expand cells from these early malignant lesions to understand this stage of malignant transformation. This is especially important since most human melanoma cell lines used today are derived either from advanced primary tumors or metastases, and have little detailed clinical annotation associated with them.