PMID- 19383809
OWN - NLM
STAT- MEDLINE
DCOM- 20090622
LR  - 20220310
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 15
IP  - 9
DP  - 2009 May 1
TI  - KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based 
      diagnostic system for ALK-positive lung cancer.
PG  - 3143-9
LID - 10.1158/1078-0432.CCR-08-3248 [doi]
AB  - PURPOSE: EML4-ALK is a transforming fusion tyrosine kinase, several isoforms of 
      which have been identified in lung cancer. Immunohistochemical detection of 
      EML4-ALK has proved difficult, however, likely as a result of low transcriptional 
      activity conferred by the promoter-enhancer region of EML4. The sensitivity of 
      EML4-ALK detection by immunohistochemistry should be increased adequately. 
      EXPERIMENTAL DESIGN: We developed an intercalated antibody-enhanced polymer 
      (iAEP) method that incorporates an intercalating antibody between the primary 
      antibody to ALK and the dextran polymer-based detection reagents. RESULTS: Our 
      iAEP method discriminated between tumors positive or negative for EML4-ALK in a 
      test set of specimens. Four tumors were also found to be positive for ALK in an 
      archive of lung adenocarcinoma (n = 130) and another 4 among fresh cases analyzed 
      in a diagnostic laboratory. These 8 tumors were found to include 1 with EML4-ALK 
      variant 1, 1 with variant 2, 3 with variant 3, and 2 with previously unidentified 
      variants (designated variants 6 and 7). Inverse reverse transcription-PCR 
      analysis revealed that the remaining tumor harbored a novel fusion in which 
      intron 24 of KIF5B was ligated to intron 19 of ALK. Multiplex reverse 
      transcription-PCR analysis of additional archival tumor specimens identified 
      another case of lung adenocarcinoma positive for KIF5B-ALK. CONCLUSIONS: The iAEP 
      method should prove suitable for immunohistochemical screening of tumors positive 
      for ALK or ALK fusion proteins among pathologic archives. Coupling of PCR-based 
      detection to the iAEP method should further facilitate the rapid identification 
      of novel ALK fusion genes such as KIF5B-ALK.
FAU - Takeuchi, Kengo
AU  - Takeuchi K
AD  - The Cancer Institute, Japanese Foundation for Cancer Research, Japan. 
      kentakeuchi-tky@umin.net
FAU - Choi, Young Lim
AU  - Choi YL
FAU - Togashi, Yuki
AU  - Togashi Y
FAU - Soda, Manabu
AU  - Soda M
FAU - Hatano, Satoko
AU  - Hatano S
FAU - Inamura, Kentaro
AU  - Inamura K
FAU - Takada, Shuji
AU  - Takada S
FAU - Ueno, Toshihide
AU  - Ueno T
FAU - Yamashita, Yoshihiro
AU  - Yamashita Y
FAU - Satoh, Yukitoshi
AU  - Satoh Y
FAU - Okumura, Sakae
AU  - Okumura S
FAU - Nakagawa, Ken
AU  - Nakagawa K
FAU - Ishikawa, Yuichi
AU  - Ishikawa Y
FAU - Mano, Hiroyuki
AU  - Mano H
LA  - eng
SI  - GENBANK/AB462411
SI  - GENBANK/AB462412
SI  - GENBANK/AB462413
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090421
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (EML4-ALK fusion protein, human)
RN  - 0 (KIF5B protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Polymers)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Alk protein, mouse)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 3.6.4.4 (Kinesins)
SB  - IM
MH  - 3T3 Cells
MH  - Adenocarcinoma/*enzymology
MH  - Anaplastic Lymphoma Kinase
MH  - Animals
MH  - Antibodies, Monoclonal
MH  - Carcinoma, Non-Small-Cell Lung/*enzymology
MH  - Cell Transformation, Neoplastic
MH  - Fibroblasts/cytology/metabolism
MH  - Genetic Variation
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Kinesins/genetics/*metabolism
MH  - Lung Neoplasms/*enzymology
MH  - Mice
MH  - Mice, Nude
MH  - Molecular Sequence Data
MH  - Oncogene Proteins, Fusion/genetics/*metabolism
MH  - Polymers/chemistry
MH  - Prognosis
MH  - Protein-Tyrosine Kinases/genetics/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptor Protein-Tyrosine Kinases
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2009/04/23 09:00
MHDA- 2009/06/23 09:00
CRDT- 2009/04/23 09:00
PHST- 2009/04/23 09:00 [entrez]
PHST- 2009/04/23 09:00 [pubmed]
PHST- 2009/06/23 09:00 [medline]
AID - 1078-0432.CCR-08-3248 [pii]
AID - 10.1158/1078-0432.CCR-08-3248 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2009 May 1;15(9):3143-9. doi: 10.1158/1078-0432.CCR-08-3248. 
      Epub 2009 Apr 21.