RET, ROS1 and ALK fusions in lung cancer

  • Nat Med. 2012 Feb 12;18(3):378-81. doi: 10.1038/nm.2658.
Kengo Takeuchi  1 ,  Manabu Soda ,  Yuki Togashi ,  Ritsuro Suzuki ,  Seiji Sakata ,  Satoko Hatano ,  Reimi Asaka ,  Wakako Hamanaka ,  Hironori Ninomiya ,  Hirofumi Uehara ,  Young Lim Choi ,  Yukitoshi Satoh ,  Sakae Okumura ,  Ken Nakagawa ,  Hiroyuki Mano ,  Yuichi Ishikawa
Affiliations
  • 1. Pathology Project for Molecular Targets, the Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. [email protected]
PMID: 22327623 DOI: 10.1038/nm.2658
Abstract

Through an integrated molecular- and histopathology-based screening system, we performed a screening for fusions of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1, receptor tyrosine kinase (ROS1) in 1,529 lung cancers and identified 44 ALK-fusion-positive and 13 ROS1-fusion-positive adenocarcinomas, including for unidentified fusion partners for ROS1. In addition, we discovered previously unidentified kinase fusions that may be promising for molecular-targeted therapy, Kinesin family member 5B (KIF5B)-ret proto-oncogene (RET) and coiled-coil domain containing 6 (CCDC6)-RET, in 14 adenocarcinomas. A multivariate analysis of 1,116 adenocarcinomas containing these 71 kinase-fusion-positive adenocarcinomas identified four independent factors that are indicators of poor prognosis: age ≥ 50 years, male sex, high pathological stage and negative kinase-fusion status.