Kyrgidis Athanassios, Tzellos Thrasivoulos-George, Triaridis Stefanos
Department of Otolaryngology, Head & Neck Surgery, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
J Carcinog. 2010 Apr 1;9:3. doi: 10.4103/1477-3163.62141.
The classification and prognostic assessment of melanoma is currently based on morphologic and histopathologic biomarkers. Availability of an increasing number of molecular biomarkers provides the potential for redefining diagnostic and prognostic categories and utilizing pharmacogenomics for the treatment of patients. The aim of the present review is to provide a basis that will allow the construction-or reconstruction-of future melanoma research.
We critically review the common medical databases (PubMed, EMBASE, Scopus and Cochrane CENTRAL) for studies reporting on molecular biomarkers for melanoma. Results are discussed along the hallmarks proposed for malignant transformation by Hanahan and Weinberg. We further discuss the genetic basis of melanoma with regard to the possible stem cell origin of melanoma cells and the role of sunlight in melanoma carcinogenesis.
Melanocyte precursors undergo several genome changes -UV-induced or not- which could be either mutations or epigenetic. These changes provide stem cells with abilities to self-invoke growth signals, to suppress antigrowth signals, to avoid apoptosis, to replicate without limit, to invade, proliferate and sustain angiogenesis. Melanocyte stem cells are able to progressively collect these changes in their genome. These new potential functions, drive melanocyte precursors to the epidermis were they proliferate and might cause benign nevi. In the epidermis, they are still capable of acquiring new traits via changes to their genome. With time, such changes could add up to transform a melanocyte precursor to a malignant melanoma stem cell.
Melanoma cannot be considered a "black box" for researchers anymore. Current trends in the diagnosis and prognosis of melanoma are to individualize treatment based on molecular biomarkers. Pharmacogenomics constitute a promising field with regard to melanoma patients' treatment. Finally, development of novel monoclonal antibodies is expected to complement melanoma patient care while a number of investigational vaccines could find their way into everyday oncology practice.
黑色素瘤的分类和预后评估目前基于形态学和组织病理学生物标志物。越来越多分子生物标志物的出现为重新定义诊断和预后类别以及利用药物基因组学治疗患者提供了潜力。本综述的目的是提供一个基础，以便构建或重建未来的黑色素瘤研究。
我们严格审查了常见医学数据库（PubMed、EMBASE、Scopus和Cochrane CENTRAL）中关于黑色素瘤分子生物标志物的研究报告。根据Hanahan和Weinberg提出的恶性转化特征对结果进行了讨论。我们还进一步讨论了黑色素瘤的遗传基础，涉及黑色素瘤细胞可能的干细胞起源以及阳光在黑色素瘤致癌过程中的作用。
黑色素细胞前体经历了多种基因组变化——无论是否由紫外线诱导——这些变化可能是突变或表观遗传变化。这些变化赋予干细胞自我激活生长信号、抑制抗生长信号、避免凋亡、无限复制、侵袭、增殖和维持血管生成的能力。黑色素干细胞能够在其基因组中逐渐积累这些变化。这些新的潜在功能驱使黑色素细胞前体到达表皮，在那里它们增殖并可能导致良性痣。在表皮中，它们仍然能够通过基因组变化获得新特性。随着时间的推移，这些变化可能累积起来，将黑色素细胞前体转化为恶性黑色素瘤干细胞。
对研究人员来说，黑色素瘤不再被视为一个“黑匣子”。黑色素瘤诊断和预后的当前趋势是基于分子生物标志物进行个体化治疗。药物基因组学在黑色素瘤患者治疗方面是一个有前景的领域。最后，新型单克隆抗体的开发有望补充黑色素瘤患者的护理，同时一些研究性疫苗可能会进入日常肿瘤学实践。
