PMID- 34372873
OWN - NLM
STAT- MEDLINE
DCOM- 20220110
LR  - 20220110
IS  - 1746-1596 (Electronic)
IS  - 1746-1596 (Linking)
VI  - 16
IP  - 1
DP  - 2021 Aug 9
TI  - Characterization of an ETV6-NTRK3 rearrangement with unusual, but highly 
      significant FISH signal pattern in a secretory carcinoma of the salivary gland: a 
      case report.
PG  - 73
LID - 10.1186/s13000-021-01133-z [doi]
LID - 73
AB  - BACKGROUND: Fusions of neurotrophic tropomyosin receptor kinase genes NTRK1, 
      NTRK2 and NTRK3 with various partner genes occur in both common and rare tumours 
      and are of paramount predictive value due to the availability of very effective 
      pan-Trk inhibitors like Larotrectinib and Entrectinib. Detection of NTRK fusions 
      is mainly performed by fluorescence in situ hybridization (FISH) and next 
      generation sequencing (NGS). The case described here showed a very unusual, but 
      highly significant FISH signal pattern with an NTRK3 break apart probe, 
      indicative of a functional NTRK3 rearrangement. CASE PRESENTATION: We describe 
      here the case of a male patient who was originally diagnosed with an 
      adenocarcinoma of the parotid gland without evidence of metastases. After the 
      development of multiple lung metastases, an extensive immunohistochemical and 
      molecular examination of archived tumour tissue including analysis of NTRK was 
      performed. NTRK expression was detected by immunohistochemistry (IHC) and then 
      comprehensively analysed further by FISH, quantitative reverse transcription PCR 
      (RT-qPCR), and NGS. NTRK3 break apart FISH showed multiple and very faint single 
      3' signals in addition to fusion signals. Quantitative reverse transcription PCR 
      and NGS confirmed an ETV6:exon5-NTRK3:exon15 fusion. Diagnosis was therefore 
      revised to metastatic secretory carcinoma of the salivary gland, and the patient 
      subsequently treated with Larotrectinib, resulting in persisting partial 
      remission. CONCLUSIONS: Our findings underline the importance to be aware of 
      non-canonical signal patterns during FISH analysis for detection of NTRK 
      rearrangements. Very faint single 3' signals can indicate a functional NTRK 
      rearrangement and therefore be of high predictive value.
CI  - (c) 2021. The Author(s).
FAU - Wagner, Florian
AU  - Wagner F
AUID- ORCID: 0000-0002-6291-7178
AD  - Zytomed Systems GmbH, Berlin, Germany. wagner@zytomed-systems.de.
FAU - Greim, Ralf
AU  - Greim R
AD  - Zytomed Systems GmbH, Berlin, Germany.
FAU - Krebs, Kathrin
AU  - Krebs K
AD  - Zytomed Systems GmbH, Berlin, Germany.
FAU - Luebben, Finn
AU  - Luebben F
AD  - Medizinische Klinik 2, Hamatologie, Onkologie, Immunologie, Palliativmedizin, St. 
      Vincentius-Kliniken Karlsruhe, ViDia Christliche Kliniken, Karlsruhe, Germany.
FAU - Dimmler, Arno
AU  - Dimmler A
AD  - Institut und Gemeinschaftspraxis fur Pathologie, St. Vincentius-Kliniken 
      Karlsruhe, ViDia Christliche Kliniken, Karlsruhe, Germany.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20210809
PL  - England
TA  - Diagn Pathol
JT  - Diagnostic pathology
JID - 101251558
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (ETV6-NTRK3 fusion protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
SB  - IM
MH  - Adenocarcinoma/diagnosis/*genetics
MH  - Adult
MH  - Biomarkers, Tumor/*genetics
MH  - *Gene Rearrangement
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Male
MH  - Oncogene Fusion
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Parotid Neoplasms/diagnosis/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC8353763
OTO - NOTNLM
OT  - Case report
OT  - ETV6-NTRK3 fusion
OT  - NTRK3 break apart FISH
OT  - Salivary gland
OT  - Secretory carcinoma
COIS- FW, RG and KK are employees of Zytomed Systems, a distributor of ZytoVision and 
      Amoy Diagnostics reagents and kits in Germany.
EDAT- 2021/08/11 06:00
MHDA- 2022/01/11 06:00
PMCR- 2021/08/09
CRDT- 2021/08/10 05:35
PHST- 2021/01/29 00:00 [received]
PHST- 2021/07/24 00:00 [accepted]
PHST- 2021/08/10 05:35 [entrez]
PHST- 2021/08/11 06:00 [pubmed]
PHST- 2022/01/11 06:00 [medline]
PHST- 2021/08/09 00:00 [pmc-release]
AID - 10.1186/s13000-021-01133-z [pii]
AID - 1133 [pii]
AID - 10.1186/s13000-021-01133-z [doi]
PST - epublish
SO  - Diagn Pathol. 2021 Aug 9;16(1):73. doi: 10.1186/s13000-021-01133-z.