RET fusions as primary oncogenic drivers and secondary acquired resistance to EGFR tyrosine kinase inhibitors in patients with non-small-cell lung cancer

Autor: Chunyue Wang, Zhenlong Zhang, Yulan Sun, Song Wang, Mengmeng Wu, Qiuxiang Ou, Yang Xu, Zhiming Chen, Yang Shao, Hong Liu, Peifeng Hou
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Translational Medicine, Vol 20, Iss 1, Pp 1-13 (2022)
Druh dokumentu: article
ISSN: 1479-5876
DOI: 10.1186/s12967-022-03593-3
Popis: Abstract Background RET fusions are rare oncogenic drivers in non-small cell lung cancer (NSCLC). While activating RET rearrangements are found in NSCLC patients harboring epidermal growth factor receptor (EGFR) genetic alterations at resistance to EGFR inhibitors, the extent to which co-occurring genomic alterations exist and how they might affect prognosis or therapy response is poorly understood. Methods Targeted next-generation sequencing (NGS) was used to assess 380 baseline patients with primary RET fusions and 71 EGFR-mutated NSCLC patients who acquired RET fusions after developing resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Results Primary RET fusions were more likely associated with females and younger age, with KIF5B being the predominant fusion partner. In baseline patients, both SMAD4 (5.3% vs. 0.0%, P = 0.044) and MYC copy-number gain variants (6.9% vs. 0.0%, P = 0.009) were more frequently co-mutated with KIF5B-RET than CCDC6-RET. By contrast, CDKN2A (11.3% vs. 2.4%, P = 0.003) mutations were significantly enriched in CCDC6-RET-rearranged baseline patients. A significant increase in the proportion of CCDC6-RET was observed in acquired RET-rearranged patients (47.3% vs. 22.5%, P
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