Clinicopathologic characteristics, genetic variability and therapeutic options of RET rearrangements patients in lung adenocarcinoma. (November 2016)

• Record Type: Journal Article
• Authors: Song, Zhengbo; Yu, Xinmin; Zhang, Yiping
• Is Part Of: Lung cancer. Volume 101(2016)
• Page Start: 16
• Page End: 21
• Publication Date: 2016-11
• Subjects: Non-small cell lung cancer -- RET -- Thymidylate synthetase -- Survival; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2016.09.002
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Eleven cases with RET arrangements were identified from 615 patients with lung adenocarcinoma. Four of eleven patients with RET arrangements harbored concurrent genes. RET rearrangements were associated with lepidic predominant lung adenocarcinoma subtype. Level of thymidylate synthetase was lower in RET-positive patients than those with RET-negative. Abstract: Background: 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. Patients and methods: 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. Results: Twelve RET-positive patients were identified by RT-PCR. However, one patient failed the detection of RET rearrangement 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 rearrangements 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 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). Conclusion: The prevalence of RET fusion is approximately 1.8% in Chinese patients with lung adenocarcinoma. RET rearrangements are characterized by lepidic predominance and a lower TS level. RET-rearranged patients may benefit more from pemetrexed-based regimen.