Tzu-Hsiu Tsai1, Shang-Gin Wu2, Min-Shu Hsieh3, Chong-Jen Yu1, James Chih-Hsin Yang4, Jin-Yuan Shih5. 1. Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. 2. Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan. 3. Department of Pathology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. 4. Department of Oncology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan. 5. Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: jyshih@ntu.edu.tw.
Abstract
OBJECTIVES: RET rearrangements represent one of the newest molecular targets in non-small cell lung cancer (NSCLC). However, the prevalence, clinical characteristics, and outcome of patients with RET-rearranged lung adenocarcinoma in metastatic disease remain uncertain. MATERIALS AND METHODS: Multiplex reverse transcription-polymerase chain reaction (RT-PCR) was used to detect KIF5B-RET and CCDC6-RET fusions from specimens of malignant pleural effusion (MPE) in patients with metastatic lung adenocarcinoma. The demographic data and outcome of patients with RET-rearranged tumors were compared with those with EGFR-mutant, KRAS-mutant, EML4-ALK-rearranged, and quadri-negative tumors. RESULTS: Of the 722 patients with MPE of lung adenocarcinoma screened, 17 (2.4%) had RET-rearranged tumors. The detected RET rearrangements comprised 11 (65%) KIF5B-RET and 6 (35%) CCDC6-RET fusions, including 2 novel fusion variants identified. The presence of RET rearrangements was not associated with age at diagnosis, gender or smoking history, but predominantly seen in solid histological subtype. None of patients with RET-rearranged tumors had received kinase inhibitors with activity against RET kinase. The median overall survival was 22.4 months (95% CI, 8.8-36.0) for the 17 patients with RET-rearranged tumors, compared with 21.3 months (95% CI, 18.7-23.9; P=0.57) for the 451 patients with EGFR-mutant tumors, 5.4 months (95% CI, 2.7-8.1; P=0.002) for the 13 patients with KRAS-mutant tumors, 18.9 months (95% CI, 10.7-27.1; P=0.82) for the 51 patients with EML4-ALK-rearranged tumors, and 12.0 months (95% CI, 9.0-15.0; P=0.07) for the 190 patients with quadri-negative tumors. CONCLUSION: Multiplex RT-PCR from specimens of MPE is feasible for the screening of RET rearrangements in NSCLC. Metastatic RET-rearranged lung adenocarcinoma patients with MPE might have favorable survival comparable to those with metastatic EGFR-mutant tumors.
OBJECTIVES:RET rearrangements represent one of the newest molecular targets in non-small cell lung cancer (NSCLC). However, the prevalence, clinical characteristics, and outcome of patients with RET-rearranged lung adenocarcinoma in metastatic disease remain uncertain. MATERIALS AND METHODS: Multiplex reverse transcription-polymerase chain reaction (RT-PCR) was used to detect KIF5B-RET and CCDC6-RET fusions from specimens of malignant pleural effusion (MPE) in patients with metastatic lung adenocarcinoma. The demographic data and outcome of patients with RET-rearranged tumors were compared with those with EGFR-mutant, KRAS-mutant, EML4-ALK-rearranged, and quadri-negative tumors. RESULTS: Of the 722 patients with MPE of lung adenocarcinoma screened, 17 (2.4%) had RET-rearranged tumors. The detected RET rearrangements comprised 11 (65%) KIF5B-RET and 6 (35%) CCDC6-RET fusions, including 2 novel fusion variants identified. The presence of RET rearrangements was not associated with age at diagnosis, gender or smoking history, but predominantly seen in solid histological subtype. None of patients with RET-rearranged tumors had received kinase inhibitors with activity against RET kinase. The median overall survival was 22.4 months (95% CI, 8.8-36.0) for the 17 patients with RET-rearranged tumors, compared with 21.3 months (95% CI, 18.7-23.9; P=0.57) for the 451 patients with EGFR-mutant tumors, 5.4 months (95% CI, 2.7-8.1; P=0.002) for the 13 patients with KRAS-mutant tumors, 18.9 months (95% CI, 10.7-27.1; P=0.82) for the 51 patients with EML4-ALK-rearranged tumors, and 12.0 months (95% CI, 9.0-15.0; P=0.07) for the 190 patients with quadri-negative tumors. CONCLUSION: Multiplex RT-PCR from specimens of MPE is feasible for the screening of RET rearrangements in NSCLC. Metastatic RET-rearranged lung adenocarcinomapatients with MPE might have favorable survival comparable to those with metastatic EGFR-mutant tumors.
Authors: Qingling Huang; Valentina E Schneeberger; Noreen Luetteke; Chengliu Jin; Roha Afzal; Mikalai M Budzevich; Rikesh J Makanji; Gary V Martinez; Tao Shen; Lichao Zhao; Kar-Ming Fung; Eric B Haura; Domenico Coppola; Jie Wu Journal: Mol Cancer Ther Date: 2016-08-05 Impact factor: 6.261