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Tropomyosin-Related Kinase Fusions in Gastrointestinal Stromal Tumors

Authors
 Ji Hyun Lee  ;  Su-Jin Shin  ;  Eun-Ah Choe  ;  Jungyoun Kim  ;  Woo Jin Hyung  ;  Hyo Song Kim  ;  Minkyu Jung  ;  Seung-Hoon Beom  ;  Tae Il Kim  ;  Joong Bae Ahn  ;  Hyun Cheol Chung  ;  Sang Joon Shin 
Citation
 CANCERS, Vol.14(11) : 2659, 2022-05 
Journal Title
CANCERS
Issue Date
2022-05
Keywords
KIT ; PDGF receptor tyrosine kinase ; gastrointestinal stromal tumor ; neurotrophic tyrosine receptor kinase fusion ; tropomyosin-related kinase fusion
Abstract
The canonical mutations in gastrointestinal stromal tumors (GISTs) are typically activating mutations in KIT and platelet-derived growth factor receptor alpha (PDGFRA). GISTs with non-canonical mutations are a heterogeneous group. Here, we examined tropomyosin-related kinase (TRK) fusion in GIST cases without KIT/PDGFRA mutations (KIT/PDGFRA wild-type (WT) GISTs). We retrospectively analyzed patients who were diagnosed with GISTs at the Yonsei Cancer Center, Severance Hospital, between January 1998 and December 2016. Thirty-one patients with KIT/PDGFRA WT GISTs were included in the analysis. TRK expression in tumor samples was assessed by pan-TRK immunohistochemistry (IHC), and the neurotrophic tyrosine receptor kinase (NTRK: the gene encoding TRK) rearrangement was analyzed by fluorescence in situ hybridization (FISH). IHC analyses revealed that five cases in this cohort exhibited a weak to moderate TRK expression. NTRK1 fusions were detected in three tumor samples, and two samples harbored NTRK3 fusions. The remaining 26 samples did not harbor NTRK fusions. Two types of NTRK fusions were detected, and the overall NTRK fusion frequency in KIT/PDGFRA WT GIST cases was 16% (5/31). Our data provide insights into the molecular alterations underpinning KIT/PDGFRA WT GISTs. More effort should be devoted to improve methods to identify this distinct disease subtype within the KIT/PDGFRA WT GIST group.
Files in This Item:
T202202040.pdf Download
DOI
10.3390/cancers14112659
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Beom, Seung Hoon(범승훈) ORCID logo https://orcid.org/0000-0001-7036-3753
Shin, Sang Joon(신상준) ORCID logo https://orcid.org/0000-0001-5350-7241
Shin, Su Jin(신수진) ORCID logo https://orcid.org/0000-0001-9114-8438
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Choe, Eun Ah(최은아) ORCID logo https://orcid.org/0000-0001-7700-8711
Hyung, Woo Jin(형우진) ORCID logo https://orcid.org/0000-0002-8593-9214
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188630
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