Petaccia de Macedo Mariana, Toledo Nascimento Ellen Caroline, Soares Fernando Augusto, Costa Santini Fernando, D'Almeida Costa Felipe, Werneck da Cunha Isabela, Ramella Munhoz Rodrigo, De Marchi Pedro, Carnier Jorge Thiago William, Ramos Moreira Leite Kátia
Rede D'Or São Luiz, São Paulo, Brazil.
D'Or Institute for Research and Teaching (IDOR), São Paulo, Brazil.
Clin Pathol. 2023 Sep 15;16:2632010X231197080. doi: 10.1177/2632010X231197080. eCollection 2023 Jan-Dec.
Oncogenic neurotrophic tropomyosin receptor kinase gene fusions occur in less than 1% of common cancers. These mutations have emerged as new biomarkers in cancer genomic profiling with the approval of selective drugs against tropomyosin receptor kinase fusion proteins. Nevertheless, the optimal pathways and diagnostic platforms for this biomarker's screening and genomic profiling have not been defined and remain a subject of debate. A panel of national experts in molecular cancer diagnosis and treatment was convened by videoconference and suggested topics to be addressed in the literature review. The authors proposed a testing algorithm for oncogenic neurotrophic tropomyosin receptor kinase gene fusion screening and diagnosis for the Brazilian health system. This review aims to discuss the latest literature evidence and international consensus on neurotrophic tropomyosin receptor kinase gene fusion diagnosis to devise clinical guidelines for testing this biomarker. We propose an algorithm in which testing for this biomarker should be requested to diagnose advanced metastatic tumors without known driver mutations. In this strategy, Immunohistochemistry should be used as a screening test followed by confirmatory next-generation sequencing in immunohistochemistry-positive cases.
致癌性神经营养性原肌球蛋白受体激酶基因融合在不到1%的常见癌症中出现。随着针对原肌球蛋白受体激酶融合蛋白的选择性药物获批，这些突变已成为癌症基因组分析中的新生物标志物。然而，用于该生物标志物筛查和基因组分析的最佳途径和诊断平台尚未确定，仍是一个有争议的话题。通过视频会议召集了一组分子癌症诊断与治疗领域的国家专家，并提出了文献综述中要探讨的主题。作者为巴西卫生系统提出了一种致癌性神经营养性原肌球蛋白受体激酶基因融合筛查与诊断的检测算法。本综述旨在讨论关于神经营养性原肌球蛋白受体激酶基因融合诊断的最新文献证据和国际共识，以制定检测该生物标志物的临床指南。我们提出一种算法，即对于无已知驱动突变的晚期转移性肿瘤诊断，应要求检测该生物标志物。在这一策略中，免疫组织化学应用作筛查试验，免疫组织化学阳性病例随后进行验证性的二代测序。
