PMID- 36612101
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230111
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 15
IP  - 1
DP  - 2022 Dec 23
TI  - GISTs with NTRK Gene Fusions: A Clinicopathological, Immunophenotypic, and 
      Molecular Study.
LID - 10.3390/cancers15010105 [doi]
LID - 105
AB  - The most common mutations in gastrointestinal stromal tumors (GISTs) are KIT or 
      PDGFRA mutations. Recently, neurotrophic tyrosine receptor kinase (NTRK) fusions 
      have been reported in WT GISTs, which increased interest in introducing 
      tropomyosin receptor kinase (TRK) inhibitors as treatments for GISTs with NTRK 
      fusions. Hence, we aimed to screen NTRK fusions in WT GISTs; we used fluorescence 
      in situ hybridization (FISH), next-generation sequencing (NGS), and 
      immunohistochemistry (IHC) to screen NTRK fusions in 46 WT GISTs and evaluate 
      each method. We further reviewed NTRK fusion-positive GISTs from the literature 
      and performed clinical and pathological analyses; two GISTs with an ETV6-NTRK3 
      fusion (5%) were identified, while only one (50%) was positive for Pan-TRK 
      expression. On the other hand, among the six GISTs with Pan-TRK-positive 
      expression, only one (17%) harbored NTRK fusion. The literature review revealed 
      the strong consistency between FISH and NGS and the limited value of Pan-TRK IHC 
      in screening NTRK fusions in GISTs. In addition, the clinical and pathological 
      analysis showed that GISTs with NTRK rearrangement occurred less frequently in 
      the stomach, were more frequently larger in size, and the epithelioid type 
      presented with a higher risk of recurrence. The NTRK3 fusion has been more common 
      than the NTRK1 fusion in GISTs to date; our study identified two ETV6-NTRK3 
      fusions in 46 WT GISTs. Compared with FISH and IHC, NGS is preferred for 
      screening WT GISTs, including NTRK rearrangements. However, since GISTs with NTRK 
      fusions are rare, further studies including more samples and mechanistic 
      investigations should be conducted in the future.
FAU - Cao, Zi
AU  - Cao Z
AD  - Department of Pathology, Tianjin Medical University Cancer Institute and 
      Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer 
      Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 
      300202, China.
FAU - Li, Jiaxin
AU  - Li J
AD  - Department of Pathology, Tianjin Medical University Cancer Institute and 
      Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer 
      Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 
      300202, China.
FAU - Sun, Lin
AU  - Sun L
AD  - Department of Pathology, Tianjin Medical University Cancer Institute and 
      Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer 
      Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 
      300202, China.
FAU - Xu, Zanmei
AU  - Xu Z
AUID- ORCID: 0000-0001-5012-6494
AD  - Shanghai OrigiMed Co., Ltd., Shanghai 201112, China.
FAU - Ke, Yan
AU  - Ke Y
AD  - Shanghai OrigiMed Co., Ltd., Shanghai 201112, China.
FAU - Shao, Bing
AU  - Shao B
AD  - Department of Pathology, Tianjin Medical University Cancer Institute and 
      Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer 
      Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 
      300202, China.
FAU - Guo, Yuhong
AU  - Guo Y
AD  - Department of Pathology, Tianjin Medical University Cancer Institute and 
      Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer 
      Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 
      300202, China.
FAU - Sun, Yan
AU  - Sun Y
AUID- ORCID: 0000-0001-8916-9598
AD  - Department of Pathology, Tianjin Medical University Cancer Institute and 
      Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer 
      Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 
      300202, China.
LA  - eng
GR  - 81871990/National Natural Science Foundation of China/
GR  - TJYXZDXK-012A/Tianjin Key Medical Discipline (Pathology) Construction Project/
GR  - 1902/Project of Tumor Translational Medicine Seed Fund of the Tianjin Medical 
      University Cancer In-stitute and Hospital/
PT  - Journal Article
DEP - 20221223
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9817796
OTO - NOTNLM
OT  - ETV6-NTRK3
OT  - gastrointestinal stromal tumor
OT  - gene fusion
OT  - neurotrophic tyrosine receptor kinase
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/09 06:00
MHDA- 2023/01/09 06:01
PMCR- 2022/12/23
CRDT- 2023/01/08 01:07
PHST- 2022/11/01 00:00 [received]
PHST- 2022/12/16 00:00 [revised]
PHST- 2022/12/19 00:00 [accepted]
PHST- 2023/01/08 01:07 [entrez]
PHST- 2023/01/09 06:00 [pubmed]
PHST- 2023/01/09 06:01 [medline]
PHST- 2022/12/23 00:00 [pmc-release]
AID - cancers15010105 [pii]
AID - cancers-15-00105 [pii]
AID - 10.3390/cancers15010105 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Dec 23;15(1):105. doi: 10.3390/cancers15010105.