Screening for the FIG-ROS1 fusion in biliary tract carcinomas by nested PCR

Genes Chromosomes Cancer. 2014 Dec;53(12):1033-40. doi: 10.1002/gcc.22212. Epub 2014 Sep 18.

Abstract

ROS1 rearrangements have been detected in a variety of tumors and are considered as suitable targets of anticancer therapies. We developed a new, quick, specific, and sensitive PCR test to screen for the FIG-ROS1 fusion and applied it to a series of Italian patients with bile duct carcinoma (BTC). Formalin-fixed, paraffin-embedded tissues, derived from 65 Italian BTC patients, and six cell lines were analyzed by nested PCR to investigate the prevalence of a previously reported FIG-ROS1 fusion. The specificity and sensitivity of nested PCR were investigated in FIG-ROS1 positive U118MG cells in reconstitution experiments with peripheral blood mononuclear cells. We found that six out of 65 (9%) BTC patients were positive for the FIG-ROS1 fusion, comprising two out of 14 (14%) gallbladder carcinoma (GBC) patients and four out of 25 (16%) extrahepatic cholangiocarcinoma (ECC) patients. None of the 26 intrahepatic cholangiocarcinoma cases harbored the FIG-ROS1 fusion. All the cell lines were negative for this variant. In conclusion, 14-16% of GBC and ECC were positive for FIG-ROS1. This may have clinical implications, since these patients will potentially benefit from the treatment with specific ROS1 inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / pathology
  • Carcinoma / pathology*
  • Cell Line, Tumor
  • Humans
  • Oncogene Proteins, Fusion / genetics*
  • Polymerase Chain Reaction
  • Sensitivity and Specificity

Substances

  • FIG-ROS1 fusion protein, human
  • Oncogene Proteins, Fusion