Lin Jianzhen, Dong Kun, Bai Yi, Zhao Songhui, Dong Yonghong, Shi Junping, Shi Weiwei, Long Junyu, Yang Xu, Wang Dongxu, Yang Xiaobo, Zhao Lin, Hu Ke, Pan Jie, Sang Xinting, Wang Kai, Zhao Haitao
Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing 100730, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Ann Transl Med. 2019 Sep;7(18):467. doi: 10.21037/atm.2019.08.67.
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.
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).
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.
The present study revealed the mutational profile for the clinical practice of precision oncology in GBC patients.
胆囊癌（GBC）是一种罕见但致命性很高的恶性肿瘤，辅助治疗有限。本研究旨在探索胆囊癌患者的可操作改变和精准肿瘤学。
纳入一线全身治疗后病情进展且病理确诊为胆囊癌的患者。通过超深度靶向二代测序（tNGS）捕获基因组改变。由多学科肿瘤委员会（MDTB）评估改变的可操作性和治疗方案。
纳入并分析了60例胆囊癌患者。所有患者均成功完成tNGS。胆囊癌患者的肿瘤突变负荷中位数为5.4（范围：0.8 - 36.74）个突变/Mb，最常见的突变发生在TP53（73%）、CDKN2A（25%）和PIK3CA（20%）。最常发生拷贝数改变的基因是CDKN2A缺失（11.7%）和ERBB2扩增（13.3%）。23%的患者出现基因融合；共鉴定出17个融合事件，其中14个融合事件与驱动基因的突变同时发生。60例患者中共有46例（76%）被确定至少有一个可操作靶点以进行精准肿瘤学治疗。
本研究揭示了胆囊癌患者精准肿瘤学临床实践的突变谱。
