Shalin Sara C
Departments of Pathology and Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Lab Invest. 2017 Feb;97(2):158-165. doi: 10.1038/labinvest.2016.122. Epub 2016 Nov 28.
Translocations resulting in a kinase fusion are well reported in many tumor types and indeed can be defining, particularly in the case of hematopoietic malignancies. The recent reports of multiple protein kinase fusions within melanocytic neoplasms, particularly in those with spitzoid morphology, have heralded a new era of classification of these melanocytic tumors. Seen within approximately half of all spitzoid neoplasms and present within the full spectrum of benign, atypical, and malignant lesions, kinase fusions likely represent an early oncogenic event contributing to cell proliferation and growth. Although the presence of a kinase fusion does not seem to correlate with the biologic potential of a given lesion, documentation of a kinase fusion will likely be important, particularly in the case of spitzoid melanoma, as numerous specific kinase receptor inhibitors have shown promise as therapeutic agents in a subset of cases with kinase fusions. Interrogation of non-spitzoid melanomas for similar kinase fusions as a potential driving oncogenic mechanism has revealed some similarities and some differences. This review will focus on the kinase fusions described to date in spitzoid neoplasms and how subsequent studies have informed current melanoma research.
导致激酶融合的易位在许多肿瘤类型中都有充分报道，实际上可能具有决定性意义，尤其是在造血系统恶性肿瘤中。最近关于黑素细胞肿瘤内多种蛋白激酶融合的报道，特别是那些具有Spitz样形态的肿瘤，开创了这些黑素细胞肿瘤分类的新时代。激酶融合见于约一半的所有Spitz样肿瘤中，且存在于良性、非典型和恶性病变的整个范围内，可能代表了促进细胞增殖和生长的早期致癌事件。尽管激酶融合的存在似乎与特定病变的生物学潜能无关，但激酶融合的记录可能很重要，特别是在Spitz样黑色素瘤的情况下，因为许多特定的激酶受体抑制剂已显示出在一部分激酶融合病例中作为治疗药物的前景。对非Spitz样黑色素瘤进行类似激酶融合的研究，作为一种潜在的驱动致癌机制，揭示了一些相似之处和一些差异。本综述将重点关注迄今为止在Spitz样肿瘤中描述的激酶融合，以及随后的研究如何为当前的黑色素瘤研究提供信息。
