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Lung Cancer |

RET Fusions Define a Unique Molecular and Clinicopathologic Subtype of NSCLC

Haichuan Hu*, MD; Rui Wang, PhD; Yunjian Pan, BS; Yihua Sun, MD; Haiquan Chen, MD
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Fudan University Cancer Center, Shanghai, China


Chest. 2012;142(4_MeetingAbstracts):593A. doi:10.1378/chest.1388972
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Abstract

SESSION TYPE: Lung Cancer II

PRESENTED ON: Monday, October 22, 2012 at 04:00 PM - 05:30 PM

PURPOSE: The RET fusion gene, which is prevalent and targetable in thyroid cancer, has been recently described in a subset of non-small-cell lung cancers (NSCLCs). As we still have limited knowledge about these tumors, this study was aimed at determining the clinicopathological characteristics of patients with NSCLCs harboring the RET fusion gene.

METHODS: We examined the RET fusion gene in 936 patients with surgical resected NSCLCs using a RT-PCR plus quantitative real-time PCR strategy. The subset of 633 patients with lung adenocarcinomas were also detected for EGFR, KRAS, HER2, BRAF mutations as well as ALK rearrangements. Patient characteristics including age, sex, smoking history, stage, grade, IASLC/ATS/ERS classification of subtypes of lung adenocarcinoma, and relapse-free survival were collected.

RESULTS: From 936 patients with NSCLCs, the RET fusion gene was exclusively detected in 13 patients (11 out of 633 patients with adenocarcinomas, and 2 out of 24 patients with adenosquamous cell carcinomas), including 9 with KIF5B-RET, 3 with CCDC6-RET, and 1 with a novel NCOA4-RET fusions. Patients with lung adenocarcinomas with RET fusion gene had more poorly differentiated tumors (63.6%, P=0.029 for RET vs. ALK, P=0.007 for RET vs. EGFR), with a tendency to younger patients (≤60, 72.7%), never smokers (81.8%), solid subtype (63.6%), and early N2 disease(54.4%). The median relapse-free survival of the patients with RET fusion positive NSCLCs was 20.5 months.

CONCLUSIONS: RET fusion occurs in 1.74% of lung adenocarcinomas and 8.33% of lung adenosquamous cell carcinomas with identifiable clinicopathological characteristics. A novel NCOA4-RET fusion detected in NSCLCs warrants further investigations.

CLINICAL IMPLICATIONS: This study determined that the patients with NSCLCs harboring RET fusion gene have identifiable clinicopathological characteristics. The further understanding of this novel molecular abnormality can be therefore introduced into future trial design and clinical managements for about 12,000 patients per year worldwide (e.g. systemic mediastinum lymphadenectomy or radiation is warranted for these patients because of their early N2 disease is frequently observed).

DISCLOSURE: The following authors have nothing to disclose: Haichuan Hu, Rui Wang, Yunjian Pan, Yihua Sun, Haiquan Chen

The screening of RET fusion gene used a RT-PCR plus quantitative real-time PCR strategy, which method is still considered research.

Fudan University Cancer Center, Shanghai, China

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