Jianzhen Lin1, Kun Dong2, Yi Bai1, Songhui Zhao3, Yonghong Dong4, Junping Shi3, Weiwei Shi3, Junyu Long1, Xu Yang1, Dongxu Wang1, Xiaobo Yang1, Lin Zhao4, Ke Hu5, Jie Pan6, Xinting Sang1, Kai Wang3,7, Haitao Zhao1. 1. Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing 100730, China. 2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China. 3. OrigiMed, Shanghai 201114, China. 4. Department of General Surgery, Shanxi Provincial People's Hospital, Taiyuan 710068, China. 5. Center for Radiotherapy, Peking Union Medical College Hospital, Beijing 100032, China. 6. Department of Radiology, Peking Union Medical College Hospital, Beijing 100032, China. 7. Zhejiang University International Hospital, Hangzhou 310030, China.
Abstract
BACKGROUND: Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy, with limited adjuvant therapy. The present study aims to explore the actionable alterations and precision oncology for GBC patients. METHODS: Patients with pathologically confirmed GBC who progressed after first-line systemic treatment were enrolled. Genomic alterations were captured by ultra-deep targeted next-generation sequencing (tNGS). The actionabilities of alterations and the therapeutic regimens were evaluated by a multidisciplinary tumor board (MDTB). RESULTS: Sixty patients with GBC were enrolled and analyzed. tNGS was successfully achieved in all patients. The median tumor mutation burden for GBC patients was 5.4 (range: 0.8-36.74) mutations/Mb, and the most common mutations were in TP53 (73%), CDKN2A (25%) and PIK3CA (20%). The most frequently copy-number altered genes were CDKN2A deletion (11.7%) and ERBB2 amplification (13.3%). 23% of the patients displayed gene fusion; 17 fusion events were identified, and 14 of the 17 fusion events co-occurred with mutations in driver genes. In total, 46 of the 60 (76%) patients were identified as possessing at least one actionable target to proceed precision oncology. CONCLUSIONS: The present study revealed the mutational profile for the clinical practice of precision oncology in GBC patients. 2019 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy, with limited adjuvant therapy. The present study aims to explore the actionable alterations and precision oncology for GBC patients. METHODS: Patients with pathologically confirmed GBC who progressed after first-line systemic treatment were enrolled. Genomic alterations were captured by ultra-deep targeted next-generation sequencing (tNGS). The actionabilities of alterations and the therapeutic regimens were evaluated by a multidisciplinary tumor board (MDTB). RESULTS: Sixty patients with GBC were enrolled and analyzed. tNGS was successfully achieved in all patients. The median tumor mutation burden for GBC patients was 5.4 (range: 0.8-36.74) mutations/Mb, and the most common mutations were in TP53 (73%), CDKN2A (25%) and PIK3CA (20%). The most frequently copy-number altered genes were CDKN2A deletion (11.7%) and ERBB2 amplification (13.3%). 23% of the patients displayed gene fusion; 17 fusion events were identified, and 14 of the 17 fusion events co-occurred with mutations in driver genes. In total, 46 of the 60 (76%) patients were identified as possessing at least one actionable target to proceed precision oncology. CONCLUSIONS: The present study revealed the mutational profile for the clinical practice of precision oncology in GBC patients. 2019 Annals of Translational Medicine. All rights reserved.
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