PMID- 33382428
OWN - NLM
STAT- MEDLINE
DCOM- 20211019
LR  - 20211019
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 106
IP  - 4
DP  - 2021 Mar 25
TI  - Pitfalls in RET Fusion Detection Using Break-Apart FISH Probes in Papillary 
      Thyroid Carcinoma.
PG  - 1129-1138
LID - 10.1210/clinem/dgaa913 [doi]
AB  - OBJECTIVE: A standardized procedure of fused REarranged during Transfection (RET) 
      gene detection using fluorescence in situ hybridization (FISH) remains to be 
      established in papillary thyroid carcinoma (PTC). Our purpose was to investigate 
      false-negative and false-positive events and their FISH signal characteristics. 
      METHODS: A total of 111 PTC cases were analyzed using break-apart FISH probes for 
      RET status evaluation. All FISH results were validated using fusion-induced 
      asymmetric transcription assay (FIATA)-based reverse transcription droplet 
      digital PCR (RT-ddPCR). Then, suspected RET-positive cases were tested using 
      quantitative reverse transcription-PCR (RT-qPCR), followed by next-generation 
      sequencing (NGS) for recognizing fusion variants. RESULTS: Thirty RET+ cases were 
      revealed, including 20 CCDC6 (exon 1)-RET (exon 12), 6 NCOA4 (exon 8)-RET (exon 
      12), 1 NCOA4 (exon 7)-RET (exon 12), 1 CCDC186 (exon 7)-RET (exon 12), 1 ERC1 
      (exon 12)-RET (exon 12) and 1 SPECC1L (exon 9)-RET (exon 12) tumors. All RET 
      fusion cases occurred in the BRAF- population, with a prevalence of 41.7% 
      (30/72). Four cases of 8% to 13% (cutoff was 7.6%) dominant isolated 3' green 
      (IG) FISH signals were RET-. One FISH- case with isolated 5' red (IR) signals 
      with 94% abnormal tumor cells was demonstrated to be positive, harboring the 
      NCOA4 (exon 7)-RET (exon 12) variant. Compared with RET fusions characterized by 
      dominant break-apart signals with 29% to 100% aberrant cells, RET + with dominant 
      IG-signal patterns all showed more frequent FISH+ cells (84%-92%). RET+ PTC with 
      a break-apart signal pattern was more frequently found in unifocal lesions than 
      in multifocal/bilateral tumors (P = 0.049). CONCLUSIONS: A false-positive or 
      false-negative event may exist for RET status detection in PTCs using the 
      traditional FISH scoring method with break-apart probes.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the 
      Endocrine Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Liu, Yuanyuan
AU  - Liu Y
AD  - Department of Pathology, Peking Union Medical College Hospital, Molecular 
      Pathology Research Center, Chinese Academy of Medical Sciences, Beijing, China.
FAU - Wu, Shafei
AU  - Wu S
AD  - Department of Pathology, Peking Union Medical College Hospital, Molecular 
      Pathology Research Center, Chinese Academy of Medical Sciences, Beijing, China.
FAU - Zhou, Liangrui
AU  - Zhou L
AD  - Department of Pathology, Peking Union Medical College Hospital, Molecular 
      Pathology Research Center, Chinese Academy of Medical Sciences, Beijing, China.
FAU - Guo, Yong
AU  - Guo Y
AD  - Department of Biomedical Engineering, School of Medicine, Tsinghua University, 
      Beijing, China.
FAU - Zeng, Xuan
AU  - Zeng X
AD  - Department of Pathology, Peking Union Medical College Hospital, Molecular 
      Pathology Research Center, Chinese Academy of Medical Sciences, Beijing, China.
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (RET protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Chromosome Aberrations
MH  - False Negative Reactions
MH  - Female
MH  - Fluorescent Dyes/analysis/metabolism
MH  - High-Throughput Nucleotide Sequencing/methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods/standards
MH  - Male
MH  - Middle Aged
MH  - Oncogene Proteins, Fusion/analysis/genetics
MH  - Predictive Value of Tests
MH  - Proto-Oncogene Proteins c-ret/analysis/*genetics
MH  - Real-Time Polymerase Chain Reaction/methods
MH  - Retrospective Studies
MH  - Thyroid Cancer, Papillary/diagnosis/*genetics
MH  - Thyroid Neoplasms/diagnosis/*genetics
MH  - Young Adult
OTO - NOTNLM
OT  - RET
OT  - FISH
OT  - false-negative
OT  - false-positive
OT  - papillary thyroid cancer
OT  - rearrangement
EDAT- 2021/01/01 06:00
MHDA- 2021/10/21 06:00
CRDT- 2020/12/31 12:07
PHST- 2020/10/23 00:00 [received]
PHST- 2021/01/01 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2020/12/31 12:07 [entrez]
AID - 6056485 [pii]
AID - 10.1210/clinem/dgaa913 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2021 Mar 25;106(4):1129-1138. doi: 
      10.1210/clinem/dgaa913.