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Poster Session (ID 8)
- Event: ACLC 2018
- Type: Poster Session
- Presentations: 1
- Coordinates: 11/07/2018, 00:00 - 00:00, Poster Hall
P081 - Clinical Characteristics and Molecular Patterns Of RET-Rearranged Lung Cancer in Chinese Patients (ID 191)
00:00 - 00:00 | Author(s): K. Zhang
Rearrangement of RET is identified as an oncogenic alteration in lung cancer. However, studies about characteristics of RET rearrangement in lung cancers are still limited, and several reports were conflicting. Our aim was to demonstrate the clinical and molecular features of RET rearrangement in Chinese lung cancers.
We reviewed genomic profiling data of biopsies (including either tissue or plasma) from 6125 lung cancer patients sequenced in a CLIA-certified laboratory from 2015 to 2017. Patient characteristics, including age, gender and histology classification were collected.
A total of 106 RET rearrangements in 84 patients (1.37%, 84/6125) were identified. RET rearrangement had a tendency to occur in female, adenocarcinoma, with a median age of 58 years. KIF5B-RET fusion was the most frequently occurred subtypes, identified in 53.8% (57/106) RET rearrangements and 67.9% (57/84) of patients, followed by CCDC6-RET and NCOA4-RET. Besides, several rare and novel RET fusion partners were identified, to the best of our knowledge, including TSSK4, SORBS1, SIRT1, PTPRK, ADD3-AS1, PRKG1, IL2RA, CCNYL2, CCDC186 and ANKS1B. We further investigated the concurrent and exclusive genomic alterations in RET-rearranged patients. TP53 was the most commonly seen concurrent mutation, occurring in 42.5% (20/47) of patients, which was followed by EGFR (14.9%, 7/47). KIF5B-RET subtype was fully mutual exclusive with EGFR mutation, suggesting that KIF5B-RET was a strong oncogenic driver mutation. RET fusion partners of the 7 patients harboring concurrent EGFR and RET rearrangement were all non-KIF5B. In addition, we observed that allelic fraction of first-generation EGFR-TKI sensitizing mutation was higher than non-KIF5B-RET in each individual patient, indicating that non-KIF5B-RET fusion might function as a potential acquired resistance mechanism to EGFR tyrosine kinase inhibitors. Clinical outcomes of cabozantinib, a RET kinase inhibitor, were available in six patients with RET-rearrangement, and the median treatment period of cabozantinib for these patients was 5 months. A stage IV adenocarcinoma patient developed resistance to osimertinib and followed NGS revealed that he harbored concurrent CCNYL2-RET fusion and EGFR mutation. After the combinatorial treatment of osimertinib and cabozantinib, he achieved stable disease (SD) with a PFS of 5 months before disease progression.
Lung cancer patients with RET-rearrangement displayed identifiable clinical characteristics and heterogeneous molecular distribution. The investigation of clinical and molecular pattern of RET-rearrangements might be helpful to provide basic knowledge for personalized diagnosis and clinical considerations. Further investigations are needed in the fields of potential sensitivities among different fusion variants and resistance mechanism to RET inhibition.