JCES01.19 Clinicopathologic Characteristics, Genetic Variability and Therapeutic Options of RET Rearrangement Patients in Lung Adenocarcinoma

Abstract

RET fusion gene is identified as a novel oncogene in a subset of non-small cell lung cancer (NSCLC). However, few data are available about the prevalence, clinicopathologic characteristics, genetic variability and therapeutic options in RET-positive lung adenocarcinoma patients. For 615 patients with lung adenocarcinoma, RET status was detected by reverse transcription-polymerase chain reaction (RT-PCR). Next-generation sequencing (NGS) and FISH were performed in positive cases. Thymidylate synthetase (TS) mRNA level was assayed by RT-PCR. Overall survival (OS) was evaluated by Kaplan-Meier method and compared with log-rank test. Twelve RET-positive patients were identified by RT-PCR. However, one patient failed the detection of RET arrangement by FISH and NGS. Totally, 11 patients (1.8%) confirmed with RET rearrangements by three methods, including six females and five males with a median age of 54 years. The presence of RET rearrangement was associated with lepidic predominant lung adenocarcinoma subtype in five of 11 patients. RET rearrangements comprised of nine KIF5B–RET and two CCDC6–RET fusions. Four patients had concurrent gene variability by NGS detection, including EGFR (n=1), MAP2K1 (n=1), CTNNB1 (n=1) and AKT1 (n=1). No survival difference existed between RET-positive and negative patients (58.1 vs. 52.0 months, P=0.504). The median progression-free survival of first-line pemetrexed/platinum regimen was 7.5 months for four recurrent cases, and longer than RET-negative patients (7.5 vs. 5.0 months, P=0.026). The level of TS mRNA was lower in RET-positive patients than that in those RET-negative counterparts (239±188×10-4 vs. 394±457×10-4, P=0.019). The prevalence of RET fusion is approximately 1.8% in Chinese patients with lung adenocarcinoma. RET arrangement is characterized by lepidic predominance and a lower TS level. RET-rearranged patients may benefit more from pemetrexed-based regimen.