PMID- 37236546
OWN - NLM
STAT- MEDLINE
DCOM- 20230801
LR  - 20230802
IS  - 1943-7811 (Electronic)
IS  - 1525-1578 (Linking)
VI  - 25
IP  - 8
DP  - 2023 Aug
TI  - Molecular and Cytogenetic Features of NTRK Fusions Enriched in BRAF and RET 
      Double-Negative Papillary Thyroid Cancer.
PG  - 569-582
LID - S1525-1578(23)00106-X [pii]
LID - 10.1016/j.jmoldx.2023.04.007 [doi]
AB  - Rare NTRK-driven malignant neoplasms can be effectively inhibited by anti-TRK 
      agents. The discovery of NTRK1/2/3-rich tumors in papillary thyroid cancer (PTC) 
      patients is a precondition for the rapid identification of NTRK fusion tumors. 
      Knowledge of NTRK gene activation is critical to accurately detect NTRK status. A 
      total of 229 BRAF V600E-negative samples from PTC patients were analyzed in this 
      study. Break-apart fluorescence in situ hybridization (FISH) was performed to 
      detect RET fusion. NTRK status was analyzed using FISH, DNA- and RNA-based 
      next-generation sequencing, and quantitative reverse transcription PCR. In 128 
      BRAF and RET double-negative cases, 56 (43.8%, 56/128) NTRK rearrangement tumors 
      were found, including 1 NTRK2, 16 NTRK1, and 39 NTRK3 fusions. Two novel NTRK 
      fusions, EZR::NTRK1 and EML4::NTRK2, were found in the NTRK rearrangement tumors. 
      Dominant break-apart and extra 3' signal patterns accounted for 89.3% (50/56) and 
      5.4% (3/56) of all NTRK-positive cases, respectively, as determined by FISH. In 
      this study's cohort, there were 2.3% (3/128) FISH false-negative and 3.1% (4/128) 
      FISH false-positive cases identified. NTRK fusions are highly recurrent in BRAF 
      and RET double-negative PTCs. FISH- or RNA-based next-generation sequencing is a 
      reliable detection approach. NTRK rearrangement can be precisely, rapidly, and 
      economically detected based on the developed optimal algorithm.
CI  - Copyright (c) 2023 Association for Molecular Pathology and American Society for 
      Investigative Pathology. Published by Elsevier Inc. All rights reserved.
FAU - Wu, Shafei
AU  - Wu S
AD  - Department of Pathology, Peking Union Medical College Hospital, and Molecular 
      Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing, China.
FAU - Liu, Yuanyuan
AU  - Liu Y
AD  - Department of Pathology, Peking Union Medical College Hospital, and Molecular 
      Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing, China.
FAU - Li, Kaimi
AU  - Li K
AD  - Department of Pathology, Peking Union Medical College Hospital, and Molecular 
      Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing, China.
FAU - Liang, Zhiyong
AU  - Liang Z
AD  - Department of Pathology, Peking Union Medical College Hospital, and Molecular 
      Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing, China. Electronic address: liangzy@pumch.cn.
FAU - Zeng, Xuan
AU  - Zeng X
AD  - Department of Pathology, Peking Union Medical College Hospital, and Molecular 
      Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing, China. Electronic address: zengx@pumch.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230525
PL  - United States
TA  - J Mol Diagn
JT  - The Journal of molecular diagnostics : JMD
JID - 100893612
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - 63231-63-0 (RNA)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (RET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.11.1 (BRAF protein, human)
SB  - IM
MH  - Humans
MH  - Thyroid Cancer, Papillary/genetics
MH  - *Receptor, trkA/genetics/analysis
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - *Thyroid Neoplasms/diagnosis/genetics/pathology
MH  - RNA
MH  - Oncogene Proteins, Fusion/genetics
MH  - Biomarkers, Tumor/genetics
MH  - Proto-Oncogene Proteins c-ret/genetics
EDAT- 2023/05/27 09:42
MHDA- 2023/08/01 06:44
CRDT- 2023/05/26 19:28
PHST- 2022/09/27 00:00 [received]
PHST- 2023/02/17 00:00 [revised]
PHST- 2023/04/10 00:00 [accepted]
PHST- 2023/08/01 06:44 [medline]
PHST- 2023/05/27 09:42 [pubmed]
PHST- 2023/05/26 19:28 [entrez]
AID - S1525-1578(23)00106-X [pii]
AID - 10.1016/j.jmoldx.2023.04.007 [doi]
PST - ppublish
SO  - J Mol Diagn. 2023 Aug;25(8):569-582. doi: 10.1016/j.jmoldx.2023.04.007. Epub 2023 
      May 25.