Malignant Progression in Human Melanoma

大约一半的人类黑色素瘤起源于被称为黑色素细胞痣的前体黑素细胞的增殖。然而，大多数黑色素细胞痣不会发生恶变，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色素细胞痣前体病变发展为原发人类黑色素瘤时，我们计划进行一项以患者为基础的研究，目标有两个。一种是更精确地定义早期原发黑色素瘤的临床特征，使用皮肤发光显微镜或皮肤镜，以可视化与皮损组织病理学相关的特定结构。另一种是从临床良性黑素细胞痣中提取黑素细胞并永生化，以研究这些细胞中的信号通路和基因表达，以更深入地了解黑素细胞转化过程中共同的第一步。这项研究的一个潜在好处是，获得了关于早期原发黑色素瘤的临床知识，结合成人黑素细胞永生化技术的发展，可能会在随后的研究中从这些早期恶性病变中获得并扩增细胞，以了解这一阶段的恶变。这一点尤其重要，因为今天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，几乎没有详细的临床注释与之相关。

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.