KIF5B-RET fusions in lung adenocarcinoma

Nat Med. 2012 Feb 12;18(3):375-7. doi: 10.1038/nm.2644.

Abstract

We identified in-frame fusion transcripts of KIF5B (the kinesin family 5B gene) and the RET oncogene, which are present in 1-2% of lung adenocarcinomas (LADCs) from people from Japan and the United States, using whole-transcriptome sequencing. The KIF5B-RET fusion leads to aberrant activation of RET kinase and is considered to be a new driver mutation of LADC because it segregates from mutations or fusions in EGFR, KRAS, HER2 and ALK, and a RET tyrosine kinase inhibitor, vandetanib, suppresses the fusion-induced anchorage-independent growth activity of NIH3T3 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Anaplastic Lymphoma Kinase
  • Animals
  • Cell Transformation, Neoplastic / drug effects
  • ErbB Receptors / genetics
  • Gene Expression Regulation, Neoplastic
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Japan
  • Kinesin / genetics*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mice
  • NIH 3T3 Cells
  • Norway
  • Oncogene Proteins, Fusion / genetics*
  • Piperidines / pharmacology
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-ret / antagonists & inhibitors
  • Proto-Oncogene Proteins c-ret / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Quinazolines / pharmacology
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor, ErbB-2 / genetics
  • United States
  • ras Proteins / genetics

Substances

  • KIF5B protein, human
  • KRAS protein, human
  • Oncogene Proteins, Fusion
  • Piperidines
  • Proto-Oncogene Proteins
  • Quinazolines
  • ALK protein, human
  • Alk protein, mouse
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Kinesin
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine