Article Abstract

Precision oncology for gallbladder cancer: insights from genetic alterations and clinical practice

Authors: Jianzhen Lin, Kun Dong, Yi Bai, Songhui Zhao, Yonghong Dong, Junping Shi, Weiwei Shi, Junyu Long, Xu Yang, Dongxu Wang, Xiaobo Yang, Lin Zhao, Ke Hu, Jie Pan, Xinting Sang, Kai Wang, Haitao Zhao


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.