Wednesday, September 15, 2021

Comprehensive identification of FGFR1-4 alterations in 5 557 Chinese patients with solid tumors by next-generation sequencing

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Am J Cancer Res. 2021 Aug 15;11(8):3893-3906. eCollection 2021.

ABSTRACT

Deregulation of fibroblast growth factor receptor (FGFR) network is common in cancer due to activating mutations, gene amplifications and chromosomal translocations. Currently, various FGFR inhibitors are being developed. In order to optimize their clinical applications, understanding the frequencies and types of FGFR alterations in multiple cancer types appears to be extremely important. This study characterized FGFR1-4 alterations in solid tumors by next-generation sequencing (NGS). Between Jun. 2019 and Aug. 2020, the sequencing data of 5 557 solid tumors of diverse types in the database of Simcere Diagnostics, Inc. (Nanjing, China) were retrospectively analyzed. A panel-based NGS assay was used to detect FGFR1-4 alterations in tumor samples. 9.2% of cancer cases had FGFR1-4 alterations, in which gene amplifications (51.5%) and mutat ions (40.7%) were frequent, whereas gene rearrangements were less common (10.0%). FGFR1 was involved in 4.6% of 5 557 cases, FGFR2 in 2.1%, FGFR3 in 1.6%, and FGFR4 in 1.4%. Of patients with FGFR1-4 alterations, TP53, MUC16, NSD3, MYC and LRP1B genes were the top 5 mutant genes. FGFR1-4 aberrations occurred in almost every type of solid tumors, with the most common tumor being endometrial carcinoma (22.2%), followed by sarcoma (17.3%), breast cancer (13.2%), gastric cancer (12.2%), and more. 0.6% of cancer cases harbored FGFR1-4 fusions, with the most common fusion partner being TACC3. Two cases of GBM harboring FGFR3-TACC3 fusions were responsive to anlotinib treatment. In conclusion, FGFR1-4 alterations are prevalent in solid tumors of diverse types, with the majority being gene amplifications and mutations. FGFR1-4 fusions only occur in a minority of cancer cases, and t hose with glioblastoma harboring FGFR3-TACC3 fusions may benefit from anlotinib.

PMID:34522456 | PMC:PMC8414391

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