PMID- 26716414
OWN - NLM
STAT- MEDLINE
DCOM- 20161220
LR  - 20211203
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 7
DP  - 2016 Feb 16
TI  - NTRK1 fusions for the therapeutic intervention of Korean patients with colon 
      cancer.
PG  - 8399-412
LID - 10.18632/oncotarget.6724 [doi]
AB  - The identification and clinical validation of cancer driver genes are essential 
      to accelerate the translational transition of cancer genomics, as well as to find 
      clinically confident targets for the therapeutic intervention of cancers. Here we 
      identified recurrent LMNA-NTRK1 and TPM3-NTRK1 fusions in Korean patients with 
      colon cancer (3 out of 147, 2%) through next-generation RNA sequencing (RNA-seq). 
      NTRK1 fusions were mutually exclusive oncogenic drivers of colon cancer that were 
      accompanied with in vitro potential of colony formation and in vivo 
      tumorigenicity comparable to KM12, a human colon cancer cell line harboring 
      TPM3-NTRK1 fusion. NTRK1-encoded TrkA protein was prevalent in 11 out of 216 
      Korean (5.1%) and 28 out of 472 Chinese patients (5.9%) from independent cohorts, 
      respectively. The expression level of TrkA was significantly correlated with 
      NTRK1 fusion (p = 0.0192), which was verified by a fluorescence in situ 
      hybridization (FISH). Korean patients with TrkA-positive colon cancer had a 
      marginal but significant shorter overall survival time than TrkA-negative colon 
      cancer [hazard ratio (HR) = 0.5346, 95% confidential interval (CI) = 
      0.2548-0.9722, p = 0.0411]. In addition, KM12 cell line was sensitive to 
      selective TrkA inhibitors. These results demonstrate that NTRK1 fusion is granted 
      as a clinically relevant target for therapeutic intervention of colon cancer.
FAU - Park, Do Youn
AU  - Park DY
AD  - Department of Pathology, Pusan National University Hospital and Pusan National 
      University School of Medicine, and BioMedical Research Institute, Pusan National 
      University Hospital, Busan, Republic of Korea.
FAU - Choi, Chan
AU  - Choi C
AD  - Department of Pathology, Chonnam National University Hwasun Hospital, Hwasun-gun, 
      Jeollanam-do, Republic of Korea.
FAU - Shin, Eunji
AU  - Shin E
AD  - LG Life Sciences Ltd., R&D Park, Daejeon, Republic of Korea.
FAU - Lee, Jae Hyuk
AU  - Lee JH
AD  - Department of Pathology, Chonnam National University Hwasun Hospital, Hwasun-gun, 
      Jeollanam-do, Republic of Korea.
FAU - Kwon, Chae Hwa
AU  - Kwon CH
AD  - Department of Pathology, Pusan National University Hospital and Pusan National 
      University School of Medicine, and BioMedical Research Institute, Pusan National 
      University Hospital, Busan, Republic of Korea.
FAU - Jo, Hong-Jae
AU  - Jo HJ
AD  - Department of Surgery, Pusan National University Hospital and Pusan National 
      University School of Medicine, and BioMedical Research Institute, Pusan National 
      University Hospital, Busan, Republic of Korea.
FAU - Kim, Hyeong-Rok
AU  - Kim HR
AD  - Department of Surgery, Chonnam National University Hwasun Hospital, Hwasun-gun, 
      Jeollanam-do, Republic of Korea.
FAU - Kim, Hyun Sung
AU  - Kim HS
AD  - Department of Surgery, Pusan National University Hospital and Pusan National 
      University School of Medicine, and BioMedical Research Institute, Pusan National 
      University Hospital, Busan, Republic of Korea.
FAU - Oh, Nahmgun
AU  - Oh N
AD  - Department of Surgery, Pusan National University Hospital and Pusan National 
      University School of Medicine, and BioMedical Research Institute, Pusan National 
      University Hospital, Busan, Republic of Korea.
FAU - Lee, Ji Shin
AU  - Lee JS
AD  - Department of Pathology, Chonnam National University Hwasun Hospital, Hwasun-gun, 
      Jeollanam-do, Republic of Korea.
FAU - Park, Ok Ku
AU  - Park OK
AD  - LG Life Sciences Ltd., R&D Park, Daejeon, Republic of Korea.
FAU - Park, Eok
AU  - Park E
AD  - LG Life Sciences Ltd., R&D Park, Daejeon, Republic of Korea.
FAU - Park, Jonghoon
AU  - Park J
AD  - LG Life Sciences Ltd., R&D Park, Daejeon, Republic of Korea.
FAU - Shin, Jong-Yeon
AU  - Shin JY
AD  - Genomic Medicine Institute (GMI), Medical Research Center, Seoul National 
      University, Seoul, Republic of Korea.
FAU - Kim, Jong-Il
AU  - Kim JI
AD  - Genomic Medicine Institute (GMI), Medical Research Center, Seoul National 
      University, Seoul, Republic of Korea.
AD  - Department of Biochemical and Molecular Biology, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
FAU - Seo, Jeong-Sun
AU  - Seo JS
AD  - Genomic Medicine Institute (GMI), Medical Research Center, Seoul National 
      University, Seoul, Republic of Korea.
AD  - Department of Biochemical and Molecular Biology, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
AD  - Macrogen Inc., Seoul, Republic of Korea.
FAU - Park, Hee Dong
AU  - Park HD
AD  - LG Life Sciences Ltd., R&D Park, Daejeon, Republic of Korea.
FAU - Park, Joonghoon
AU  - Park J
AD  - LG Life Sciences Ltd., R&D Park, Daejeon, Republic of Korea.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Carbazoles)
RN  - 0 (Furans)
RN  - 0 (LMNA protein, human)
RN  - 0 (Lamin Type A)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (TPM3 protein, human)
RN  - 0 (Tropomyosin)
RN  - 53AH36668S (Crizotinib)
RN  - DO989GC5D1 (lestaurtinib)
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Carbazoles/pharmacology
MH  - Carcinogenesis
MH  - Case-Control Studies
MH  - Colonic Neoplasms/*drug therapy/*genetics/pathology
MH  - Crizotinib
MH  - Female
MH  - Follow-Up Studies
MH  - Furans
MH  - Gene Fusion
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization, Fluorescence
MH  - Lamin Type A/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasm Staging
MH  - Oncogene Proteins, Fusion/genetics/*metabolism
MH  - Prognosis
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Pyrazoles/pharmacology
MH  - Pyridines/pharmacology
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptor, trkA/*genetics/*metabolism
MH  - Republic of Korea
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Survival Rate
MH  - Tropomyosin/genetics/metabolism
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
PMC - PMC4885001
OTO - NOTNLM
OT  - Korean colon cancer
OT  - NTRK1 fusion
OT  - RNA-seq
OT  - predictive biomarker
OT  - targeted therapy
COIS- CONFLICTS OF INTEREST D.Y.P., C.C., E.S., J.H.L., C.H.K., O.K.P. and J.P. are 
      listed on a regularized patent application filed with the Korean Intellectual 
      Property Office related to detection and use of NTRK1 fusion in cancer.
EDAT- 2015/12/31 06:00
MHDA- 2016/12/21 06:00
PMCR- 2016/02/16
CRDT- 2015/12/31 06:00
PHST- 2015/09/11 00:00 [received]
PHST- 2015/12/07 00:00 [accepted]
PHST- 2015/12/31 06:00 [entrez]
PHST- 2015/12/31 06:00 [pubmed]
PHST- 2016/12/21 06:00 [medline]
PHST- 2016/02/16 00:00 [pmc-release]
AID - 6724 [pii]
AID - 10.18632/oncotarget.6724 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Feb 16;7(7):8399-412. doi: 10.18632/oncotarget.6724.