Department of Internal Medicine, University of Connecticut Health Center, Farmington, CT 06032, USA.
Clin Dermatol. 2013 May-Jun;31(3):317-23. doi: 10.1016/j.clindermatol.2012.08.007.
With the advent of genetic and epigenetic research, molecular techniques could someday be used to discriminate nevus from melanoma so that ambiguous melanocytic lesions could be more accurately classified or that prognostication could be improved in melanoma patients. That promised day might be closer than realized. The last 20 years of research in cytogenetic and genetic alterations in melanoma have culminated in defined chromosomal lesions discriminating benign from malignant melanocytic tumors. Exploiting these differences, fluorescence in situ hybridization (FISH) can reproducibly discriminate unequivocal melanomas from melanocytic nevi with high sensitivity and specificity. The discriminating power of FISH in melanocytic tumors with ambiguous histopathology is questionable, however, because there is no standard definition of "malignancy." Additional FISH studies on ambiguous cases are needed through international collaborations where large collections of such cases are shared and the "proof of malignancy" is established by adequate clinical follow-up. This contribution reviews the diagnostic utility of DNA-based FISH technology as it compares the diagnostic accuracy in melanocytic tumors with unambiguous vs ambiguous histopathology. The melanoma epigenome is further characterized through research into various activities of small interfering RNAs, such as microRNAs, providing the pathway for the application of microRNA-based strategies that could be the basis for future diagnostic biomarkers and molecular therapies in melanoma.
随着基因和表观遗传学研究的出现，分子技术有朝一日可能被用于区分痣和黑色素瘤，以便更准确地对模棱两可的黑素细胞病变进行分类，或改善黑色素瘤患者的预后。那个承诺的日子可能比想象的要近。过去 20 年对黑色素瘤细胞遗传学和遗传改变的研究最终导致了明确的染色体病变，区分良性和恶性黑素细胞肿瘤。利用这些差异，荧光原位杂交（FISH）可以以高灵敏度和特异性重复区分明确的黑色素瘤和黑素细胞痣。然而，FISH 在具有模棱两可组织病理学的黑素细胞肿瘤中的区分能力值得怀疑，因为“恶性”没有标准定义。需要通过国际合作进行更多关于模棱两可病例的 FISH 研究，这些国际合作共享此类病例的大量集合，并且通过充分的临床随访来确定“恶性证据”。这篇综述回顾了基于 DNA 的 FISH 技术的诊断效用，因为它比较了具有明确和模棱两可组织病理学的黑素细胞肿瘤的诊断准确性。通过研究小干扰 RNA（如 microRNAs）的各种活性，进一步描述了黑色素瘤的表观基因组，为应用基于 microRNA 的策略提供了途径，这些策略可能成为未来黑色素瘤诊断生物标志物和分子治疗的基础。
