What question did this study set out to answer?

To characterize molecular features and clinical factors associated with RET fusion in NSCLC patients.

April 30, 2026Open Access

Molecular Characterisations and the Association with Clinical Factors in RET Fusion-Positive NSCLC: A Retrospective Study of the Single Center Cohort

Key Points

To characterize molecular features and clinical factors associated with RET fusion in NSCLC patients.
Retrospective cohort study of 6204 lung cancer patients from 2018 to 2024
Analysis of molecular and clinical characteristics in patients with RET fusion
Use of next-generation sequencing for detection of RET fusions
RET fusions had a prevalence of 1.6% in lung cancer cohort
Most patients were non-smokers, under 60 years, with adenocarcinoma
TP53 was the most frequent concomitant alteration in RET fusions at 14.71%

Abstract

Background: RET fusion is a pathogenic driver factor in lung cancer patients. Currently, the conclusions on the clinical factors of RET fusion in NSCLC are inconsistent. Methods: From 2018 to 2024, 6,204 lung cancer patients received next‑generation sequencing (NGS) testing, among whom 102 were confirmed to be positive for RET fusion. The clinical and molecular characteristics of these patients were analyzed and compared. Results: In this cohort, the prevalence of RET fusions was 1.6% (102/6204). Most patients were female (54.90%), < 60 years (53.92%), non-smokers (72.55%), with advanced-stage (68.63%), metastatic (69.61%, mostly lymph nodes), adenocarcinoma (98.04%), and PS 0– 1 (90.20%). The most common fusion partners of RET were KIF5B (50.00%, 51/102) and CCDC6 (22.55%, 23/102).; noval partners including C16orf95, CARNMT1-AS1, CXCL12, MTUS1 and MYRFL were identified. Common fusion partners were associated with age (P=0.023) and PS score (P=0.040), with higher rates of RET fusion in patients < 60 years of age and those with a PS score of 0– 1 (81.80% and 76.10%, respectively. TP53 represented the most frequent concomitant alteration in RET fusions, occurring at a rate of 14.71% (15/102). Conclusion: The new discoveries of RET fusion partners were founded in NSCLC. In addition, the broad-panel NGS is essential for NSCLC patients to catch these rare/novel fusions that PCR or small panels might miss. Keywords: NSCLC, RET fusion, molecular characteristics, NGS

Molecular Characterisations and the Association with Clinical Factors in RET Fusion-Positive NSCLC: A Retrospective Study of the Single Center Cohort

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Abstract

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