PMID- 32825119
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201027
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 9
DP  - 2020 Aug 19
TI  - Identification of Novel Fusion Genes in Bone and Soft Tissue Sarcoma and Their 
      Implication in the Generation of a Mouse Model.
LID - 10.3390/cancers12092345 [doi]
LID - 2345
AB  - Fusion genes induced by chromosomal aberrations are common mutations causally 
      associated with bone and soft tissue sarcomas (BSTS). These fusions are usually 
      disease type-specific, and identification of the fusion genes greatly helps in 
      making precise diagnoses and determining therapeutic directions. However, there 
      are limitations in detecting unknown fusion genes or rare fusion variants when 
      using standard fusion gene detection techniques, such as reverse 
      transcription-polymerase chain reaction (RT-PCR) and fluorescence in situ 
      hybridization (FISH). In the present study, we have identified 19 novel fusion 
      genes using target RNA sequencing (RNA-seq) in 55 cases of round or spindle cell 
      sarcomas in which no fusion genes were detected by RT-PCR. Subsequent analysis 
      using Sanger sequencing confirmed that seven out of 19 novel fusion genes would 
      produce functional fusion proteins. Seven fusion genes detected in this study 
      affect signal transduction and are ideal targets of small molecule inhibitors. 
      YWHAE-NTRK3 expression in mouse embryonic mesenchymal cells (eMCs) induced 
      spindle cell sarcoma, and the tumor was sensitive to the TRK inhibitor LOXO-101 
      both in vitro and in vivo. The combination of target RNA-seq and generation of an 
      ex vivo mouse model expressing novel fusions provides important information both 
      for sarcoma biology and the appropriate diagnosis of BSTS.
FAU - Teramura, Yasuyo
AU  - Teramura Y
AD  - Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer 
      Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
FAU - Tanaka, Miwa
AU  - Tanaka M
AD  - Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer 
      Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
FAU - Yamazaki, Yukari
AU  - Yamazaki Y
AD  - Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer 
      Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
FAU - Yamashita, Kyoko
AU  - Yamashita K
AD  - Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer 
      Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
FAU - Takazawa, Yutaka
AU  - Takazawa Y
AD  - Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer 
      Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
AD  - Department of Pathology, Toranomon Hospital, Tokyo 105-8470, Japan.
FAU - Ae, Keisuke
AU  - Ae K
AD  - Division of Orthopedic Oncology, The Cancer Institute Hospital, Japanese 
      Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
FAU - Matsumoto, Seiichi
AU  - Matsumoto S
AD  - Division of Orthopedic Oncology, The Cancer Institute Hospital, Japanese 
      Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
FAU - Nakayama, Takayuki
AU  - Nakayama T
AD  - Department of Orthopedic Surgery (Ohashi), School of Medicine, Toho University, 
      Tokyo 143-8540, Japan.
FAU - Kaneko, Takao
AU  - Kaneko T
AUID- ORCID: 0000-0002-4190-663X
AD  - Department of Orthopedic Surgery (Ohashi), School of Medicine, Toho University, 
      Tokyo 143-8540, Japan.
FAU - Musha, Yoshiro
AU  - Musha Y
AD  - Department of Orthopedic Surgery (Ohashi), School of Medicine, Toho University, 
      Tokyo 143-8540, Japan.
FAU - Nakamura, Takuro
AU  - Nakamura T
AUID- ORCID: 0000-0002-0419-7547
AD  - Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer 
      Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
LA  - eng
GR  - 26250029/Japan Society for the Promotion of Science/
GR  - 17cmA002/Japan Agency for Medical Research and Development/
PT  - Journal Article
DEP - 20200819
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7565474
OTO - NOTNLM
OT  - NTRK
OT  - bone and soft tissue sarcomas
OT  - fusion gene
OT  - inhibitor
OT  - mouse model
OT  - target RNA sequencing
COIS- The authors declare no conflict of interest.
EDAT- 2020/08/23 06:00
MHDA- 2020/08/23 06:01
PMCR- 2020/08/19
CRDT- 2020/08/23 06:00
PHST- 2020/07/02 00:00 [received]
PHST- 2020/08/14 00:00 [revised]
PHST- 2020/08/17 00:00 [accepted]
PHST- 2020/08/23 06:00 [entrez]
PHST- 2020/08/23 06:00 [pubmed]
PHST- 2020/08/23 06:01 [medline]
PHST- 2020/08/19 00:00 [pmc-release]
AID - cancers12092345 [pii]
AID - cancers-12-02345 [pii]
AID - 10.3390/cancers12092345 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Aug 19;12(9):2345. doi: 10.3390/cancers12092345.