Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies

Nat Med. 2012 Feb 12;18(3):382-4. doi: 10.1038/nm.2673.

Abstract

Applying a next-generation sequencing assay targeting 145 cancer-relevant genes in 40 colorectal cancer and 24 non-small cell lung cancer formalin-fixed paraffin-embedded tissue specimens identified at least one clinically relevant genomic alteration in 59% of the samples and revealed two gene fusions, C2orf44-ALK in a colorectal cancer sample and KIF5B-RET in a lung adenocarcinoma. Further screening of 561 lung adenocarcinomas identified 11 additional tumors with KIF5B-RET gene fusions (2.0%; 95% CI 0.8-3.1%). Cells expressing oncogenic KIF5B-RET are sensitive to multi-kinase inhibitors that inhibit RET.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Animals
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Cell Transformation, Neoplastic / drug effects
  • Colorectal Neoplasms / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Kinesin / antagonists & inhibitors
  • Kinesin / genetics*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mice
  • NIH 3T3 Cells
  • Oncogene Proteins, Fusion / genetics*
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-ret / antagonists & inhibitors
  • Proto-Oncogene Proteins c-ret / genetics*
  • Receptor Protein-Tyrosine Kinases / genetics*

Substances

  • KIF5B protein, human
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • ALK protein, human
  • Alk protein, mouse
  • Anaplastic Lymphoma Kinase
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor Protein-Tyrosine Kinases
  • Kinesin