Bridgewater John, Jiao Xiaolong, Parimi Mounika, Flach Clare, Stratford Jeran, Kamburov Atanas, Schmitz Arndt A, Zong Jihong, Reeves John A, Keating Karen, Bruno Amanda, Fellous Marc, Pereira Mariana Buongermino, Bazhenova Lyudmila
University College London Hospitals NHS Trust, London, United Kingdom; University College London Cancer Institute, London, United Kingdom.
Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, United States of America.
Cancer Treat Res Commun. 2022;33:100623. doi: 10.1016/j.ctarc.2022.100623. Epub 2022 Aug 23.
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers in various tumor types. Limited data exist on the overall survival (OS) of patients with tumors with NTRK gene fusions and on the co-occurrence of NTRK fusions with other oncogenic drivers.
This retrospective study included patients enrolled in the Genomics England 100,000 Genomes Project who had linked clinical data from UK databases. Patients who had undergone tumor whole genome sequencing between March 2016 and July 2019 were included. Patients with and without NTRK fusions were matched. OS was analyzed along with oncogenic alterations in ALK, BRAF, EGFR, ERBB2, KRAS, and ROS1, and tumor mutation burden (TMB) and microsatellite instability (MSI).
Of 15,223 patients analyzed, 38 (0.25%) had NTRK gene fusions in 11 tumor types, the most common were breast cancer, colorectal cancer (CRC), and sarcoma. Median OS was not reached in both the NTRK gene fusion-positive and -negative groups (hazard ratio 1.47, 95% CI 0.39-5.57, P = 0.572). A KRAS mutation was identified in two (5%) patients with NTRK gene fusions, and both had hepatobiliary cancer. High TMB and MSI were both more common in patients with NTRK gene fusions, due to the CRC subset. While there was a higher risk of death in patients with NTRK gene fusions compared to those without, the difference was not statistically significant.
This study supports the hypothesis that NTRK gene fusions are primary oncogenic drivers and the co-occurrence of NTRK gene fusions with other oncogenic alterations is rare.
神经营养性酪氨酸受体激酶（NTRK）基因融合是多种肿瘤类型中的致癌驱动因素。关于NTRK基因融合肿瘤患者的总生存期（OS）以及NTRK融合与其他致癌驱动因素同时出现的数据有限。
这项回顾性研究纳入了参与英国国家医疗服务体系10万基因组计划且临床数据与英国数据库相关联的患者。纳入2016年3月至2019年7月期间接受肿瘤全基因组测序的患者。对有和没有NTRK融合的患者进行匹配。分析了OS以及ALK、BRAF、EGFR、ERBB2、KRAS和ROS1的致癌改变，以及肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）。
在分析的15223例患者中，38例（0.25%）在11种肿瘤类型中存在NTRK基因融合，最常见的是乳腺癌、结直肠癌（CRC）和肉瘤。NTRK基因融合阳性和阴性组的中位OS均未达到（风险比1.47，95%CI 0.39 - 5.57，P = 0.572）。在2例（5%）NTRK基因融合患者中鉴定出KRAS突变，均为肝胆癌。由于CRC亚组，高TMB和MSI在NTRK基因融合患者中更常见。虽然与无NTRK基因融合的患者相比，有NTRK基因融合的患者死亡风险更高，但差异无统计学意义。
本研究支持以下假设，即NTRK基因融合是主要的致癌驱动因素，且NTRK基因融合与其他致癌改变同时出现的情况很少见。
