RET, ROS1 and ALK fusions in lung cancer

Kengo Takeuchi; 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

doi:10.1038/nm.2658

RET, ROS1 and ALK fusions in lung cancer

Nat Med. 2012 Feb 12;18(3):378-81. doi: 10.1038/nm.2658.

Authors

Kengo Takeuchi¹, 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

Affiliation

¹ Pathology Project for Molecular Targets, the Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. kentakeuchi-tky@umin.net

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Adenocarcinoma / genetics*
Adenocarcinoma / pathology
Adenocarcinoma of Lung
Adult
Age Factors
Aged
Aged, 80 and over
Anaplastic Lymphoma Kinase
Animals
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Transformation, Neoplastic / genetics
Cytoskeletal Proteins / genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms / genetics*
Lung Neoplasms / pathology
Male
Mice
Middle Aged
Neoplasm Staging
Oncogene Proteins, Fusion / genetics*
Piperidines / pharmacology
Prognosis
Protein-Tyrosine Kinases / genetics*
Proto-Oncogene Mas
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins c-ret / genetics*
Quinazolines / pharmacology
Receptor Protein-Tyrosine Kinases / genetics*
Sex Factors

Substances

CCDC6 protein, human
Cytoskeletal Proteins
MAS1 protein, human
Oncogene Proteins, Fusion
Piperidines
Proto-Oncogene Mas
Proto-Oncogene Proteins
Quinazolines
ALK protein, human
Alk protein, mouse
Anaplastic Lymphoma Kinase
Protein-Tyrosine Kinases
Proto-Oncogene Proteins c-ret
RET protein, human
ROS1 protein, human
Receptor Protein-Tyrosine Kinases
vandetanib