Abstract
Abstract Background: FGFR gene is a promising therapeutic target, and several inhibitors targeted FGFR have demonstrated clinical benefit in cancer patients, such as Erdafitinib in Metastatic Urothelial Cancer. However, the landscape of FGFR gene in Chinese patients with solid tumors has not been well understood, partially because the patients usually harbored different variations from other family gene members (FGFR1-4). Methods: FFPE tumor samples were collected from 3736 Chinese patients with solid tumor for NGS-based targeted panel sequencing. Patients included lung cancer (39.3%, 1467/3736), hepatocellular cancer (8.6%, 322/3736), colorectal cancer (8.6%, 322/3736), pancreatic cancer (6.9%, 260/3736), gastric cancer (5.3%, 199/3736), intrahepatic cholangiocarcinoma (5.1%, 190/3736), and others. We measured the single base substitution, short and long insertions/deletions, copy number variations, gene fusions and rearrangements in tumor tissue against matched blood. Results: In total, 6.6% of the 3736 patients with solid tumor had FGFR 1-4 variations. The incidences of genomic alterations on FGFR1, 2, 3, and 4 were 2.8%, 1.6%, 1.2% and 1%, respectively. Amplification was the most common type of FGFR variation, which accounted for 47% of all the genomic alterations, followed by mutations (41.5%) and fusions (11.4%). FGFR variations occurred in multiple cancers, among which FGFR variations were more likely to occur in uterine (4/17; 23.5%), squamous cell lung (29/167; 17.4%), breast (14/82; 17%), urothelial (2/12; 16.6%), intrahepatic cholangiocarcinoma (22/190; 11.6%), colorectal (31/322; 9.6%), gastric (16/199; 8%), small cell lung (7/93; 7.5%), pancreatic (11/260; 4.2%), and hepatocellular cancer (10/322; 3.1%). Most of these data was similar with previously reported published data or TCGA. However, compared with TCGA data, lower incidence was found in three types of cancers: Lung cancer 5.5% vs 19%; hepatocellular cancer 3.1% vs 11%; and pancreatic cancer 4.2% vs 10%. Interestingly, distribution of FGFR variations was also different between cancers. For example, in lung cancer, FGFR1 amplification was the most common variation of FGFR (2.8%), while few fusions were observed. In addition, FGFR2 fusion was mainly in intrahepatic cholangiocarcinoma (6.3%), while FGFR 1/3/4 fusions were rare. Conclusions: This study, for the first time, revealed that FGFR genomic alterations were found in approximately 6.6% of Chinese patients across different solid tumors. FGFR1 amplifications and FGFR2 fusions were detected with higher frequencies in Lung cancer and intrahepatic cholangiocarcinoma. Our results indicated FGFRinhibitors would be a potential therapeutic strategy to be considered for Chinese patients with FGFR genomic alterations. Citation Format: Kunpeng Bu, Zuping Lian, Xiangping Wang, Guoli Lv, Ruobing Ma, Qiang Cui, Ming Yao, Aodi Wang, Hui Chen, Youming Lei. The landscape of FGFR alteration in Chinese solid tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2519.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have