Chimeric transcripts observed in non-canonical FGFR2 fusions with partner genes' breakpoint located in intergenic region in intrahepatic cholangiocarcinoma

Cancer Genet. 2022 Aug:266-267:39-43. doi: 10.1016/j.cancergen.2022.06.004. Epub 2022 Jun 13.

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a fatal bile duct cancer with dismal prognosis and limited therapeutic options. FGFR family fusion have been identified in many diseases, and FGFR2 fusion is a validated oncogenic driver in ICC. At present, a variety of fusion forms have been reported, including gene-gene, gene-intergenic, and intergenic-intergenic fusion. Here, by performing RNA- and DNA-sequencing analysis, FGFR2 fusions were found in 10.1% of ICC, including 4 gene-intergenic fusions. We confirmed that the non-canonical rearrangements can generate chimeric transcripts, and used conventional splicing mechanism to explain the event. Our study provides possible target therapy for these 4 patients and possibility analysis scheme for similar situation.

Keywords: Breakpoint; FGFR2 fusion; Gene-intergenic; Intrahepatic cholangiocarcinoma; NGS.

MeSH terms

  • Bile Duct Neoplasms* / genetics
  • Bile Duct Neoplasms* / pathology
  • Bile Ducts, Intrahepatic / pathology
  • Cholangiocarcinoma* / genetics
  • Cholangiocarcinoma* / pathology
  • DNA, Intergenic
  • Humans
  • Pyrimidines / adverse effects
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics
  • Receptor, Fibroblast Growth Factor, Type 2 / therapeutic use

Substances

  • DNA, Intergenic
  • Pyrimidines
  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2