Nguyen Minh Anh, Colebatch Andrew J, Van Beek Diana, Tierney Geraldine, Gupta Ruta, Cooper Wendy A
Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Pathology. 2023 Aug;55(5):596-609. doi: 10.1016/j.pathol.2023.05.002. Epub 2023 May 26.
Fusions involving the Neurotrophic tropomyosin receptor kinase (NTRK) gene family (NTRK1, NTRK2 and NTRK3) are targetable oncogenic alterations that are found in a diverse range of tumours. There is an increasing demand to identify tumours which harbour these fusions to enable treatment with selective tyrosine kinase inhibitors such as larotrectinib and entrectinib. NTRK fusions occur in a wide range of tumours including rare tumours such as infantile fibrosarcoma and secretory carcinomas of the salivary gland and breast, as well as at low frequencies in more common tumours including melanoma, colorectal, thyroid and lung carcinomas. Identifying NTRK fusions is a challenging task given the different genetic mechanisms underlying NTRK fusions, their varying frequency across different tumour types, complicated by other factors such as tissue availability, optimal detection methods, accessibility and costs of testing methods. Pathologists play a key role in navigating through these complexities by determining optimal approaches to NTRK testing which has important therapeutic and prognostic implications. This review provides an overview of tumours harbouring NTRK fusions, the importance of identifying these fusions, available testing methods including advantages and limitations, and generalised and tumour-specific approaches to testing.
涉及神经营养性原肌球蛋白受体激酶（NTRK）基因家族（NTRK1、NTRK2和NTRK3）的融合是可靶向的致癌性改变，见于多种肿瘤。识别携带这些融合的肿瘤以使用选择性酪氨酸激酶抑制剂（如拉罗替尼和恩曲替尼）进行治疗的需求日益增加。NTRK融合见于多种肿瘤，包括罕见肿瘤，如婴儿纤维肉瘤以及唾液腺和乳腺的分泌性癌，在更常见的肿瘤如黑色素瘤、结直肠癌、甲状腺癌和肺癌中也有低频率发生。鉴于NTRK融合背后的不同遗传机制、它们在不同肿瘤类型中的不同频率，再加上诸如组织可获得性、最佳检测方法、检测方法的可及性和成本等其他因素，识别NTRK融合是一项具有挑战性的任务。病理学家通过确定NTRK检测的最佳方法在应对这些复杂性方面发挥关键作用，这具有重要的治疗和预后意义。本综述概述了携带NTRK融合的肿瘤、识别这些融合的重要性、可用的检测方法（包括优缺点）以及检测的一般方法和肿瘤特异性方法。
