PMID- 32061944
OWN - NLM
STAT- MEDLINE
DCOM- 20201027
LR  - 20201027
IS  - 1096-0945 (Electronic)
IS  - 0014-4800 (Linking)
VI  - 114
DP  - 2020 Jun
TI  - Feasibility and clinical utility of a pan-solid tumor targeted RNA fusion panel: 
      A single center experience.
PG  - 104403
LID - S0014-4800(19)30976-1 [pii]
LID - 10.1016/j.yexmp.2020.104403 [doi]
AB  - Gene fusions are caused by chromosomal rearrangements and encode fusion proteins 
      that can act as oncogenic drivers in cancers. Traditional methods for detecting 
      oncogenic fusion transcripts include fluorescence in situ hybridization (FISH), 
      reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry 
      (IHC). However, these methods are limited in scalability and pose significant 
      technical and interpretational challenges. Next-generation sequencing (NGS) is a 
      high-throughput method for detecting genetic abnormalities and providing 
      prognostic and therapeutic information for cancer patients. We present our 
      experience with the validation of a custom-designed Archer Anchored Multiplex PCR 
      (AMP) technology-based NGS technology, "NYU FUSION-SEQer" using RNA sequencing. 
      We examine both analytical performance and clinical utility of the panel using 75 
      retrospective validation samples and 84 prospective clinical samples of solid 
      tumors. Our panel showed robust sequencing performance with strong enrichment for 
      target regions. The lower limit of detection was 12.5% tumor fraction at 125 ng 
      of RNA input. The panel demonstrated excellent analytic accuracy, with 100% 
      sensitivity, 100% specificity and 100% reproducibility on validation samples. 
      Finally, in the prospective cohort, the panel detected fusions in 61% cases 
      (n = 51), out of which 41% (n = 21) enabling diagnosis and 59% (n = 30) enabling 
      treatment and prognosis. We demonstrate that the fusion panel can accurately, 
      efficiently and cost-effectively detect the majority of known fusion genes, novel 
      clinically relevant fusions and provides an excellent tool for discovery of new 
      fusion genes in solid tumors.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Hindi, Issa
AU  - Hindi I
AD  - Department of Pathology, New York University Langone Health, New York, NY, United 
      States of America.
FAU - Shen, Guomiao
AU  - Shen G
AD  - Department of Pathology, New York University Langone Health, New York, NY, United 
      States of America.
FAU - Tan, Qian
AU  - Tan Q
AD  - Department of Pathology, New York University Langone Health, New York, NY, United 
      States of America.
FAU - Cotzia, Paolo
AU  - Cotzia P
AD  - Department of Pathology, New York University Langone Health, New York, NY, United 
      States of America.
FAU - Snuderl, Matija
AU  - Snuderl M
AD  - Department of Pathology, New York University Langone Health, New York, NY, United 
      States of America.
FAU - Feng, Xiaojun
AU  - Feng X
AD  - Department of Pathology, New York University Langone Health, New York, NY, United 
      States of America.
FAU - Jour, George
AU  - Jour G
AD  - Department of Pathology, New York University Langone Health, New York, NY, United 
      States of America; Department of Dermatology, New York University Langone Health, 
      New York, NY, United States of America. Electronic address: 
      George.jour@nyulangone.org.
LA  - eng
PT  - Journal Article
DEP - 20200213
PL  - Netherlands
TA  - Exp Mol Pathol
JT  - Experimental and molecular pathology
JID - 0370711
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (RNA, Neoplasm)
SB  - IM
MH  - Biomarkers, Tumor/genetics
MH  - Female
MH  - High-Throughput Nucleotide Sequencing/*methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Multiplex Polymerase Chain Reaction/*methods
MH  - Neoplasms/*genetics/pathology
MH  - Oncogene Proteins, Fusion/genetics/*isolation & purification
MH  - RNA, Neoplasm/genetics/isolation & purification
OTO - NOTNLM
OT  - Anchored multiplex PCR
OT  - Gene fusion
OT  - RNA sequencing
OT  - Solid tumors
OT  - Targeted therapy
COIS- Declaration of Competing Interest The authors declare no conflict of interest.
EDAT- 2020/02/18 06:00
MHDA- 2020/10/28 06:00
CRDT- 2020/02/17 06:00
PHST- 2019/12/13 00:00 [received]
PHST- 2020/02/03 00:00 [revised]
PHST- 2020/02/12 00:00 [accepted]
PHST- 2020/02/18 06:00 [pubmed]
PHST- 2020/10/28 06:00 [medline]
PHST- 2020/02/17 06:00 [entrez]
AID - S0014-4800(19)30976-1 [pii]
AID - 10.1016/j.yexmp.2020.104403 [doi]
PST - ppublish
SO  - Exp Mol Pathol. 2020 Jun;114:104403. doi: 10.1016/j.yexmp.2020.104403. Epub 2020 
      Feb 13.