PMID- 24813172
OWN - NLM
STAT- MEDLINE
DCOM- 20150202
LR  - 20211021
IS  - 1943-7811 (Electronic)
IS  - 1525-1578 (Print)
IS  - 1525-1578 (Linking)
VI  - 16
IP  - 4
DP  - 2014 Jul
TI  - Detection of gene rearrangements in targeted clinical next-generation sequencing.
PG  - 405-17
LID - S1525-1578(14)00074-9 [pii]
LID - 10.1016/j.jmoldx.2014.03.006 [doi]
AB  - The identification of recurrent gene rearrangements in the clinical laboratory is 
      the cornerstone for risk stratification and treatment decisions in many malignant 
      tumors. Studies have reported that targeted next-generation sequencing assays 
      have the potential to identify such rearrangements; however, their utility in the 
      clinical laboratory is unknown. We examine the sensitivity and specificity of ALK 
      and KMT2A (MLL) rearrangement detection by next-generation sequencing in the 
      clinical laboratory. We analyzed a series of seven ALK rearranged cancers, six 
      KMT2A rearranged leukemias, and 77 ALK/KMT2A rearrangement-negative cancers, 
      previously tested by fluorescence in situ hybridization (FISH). Rearrangement 
      detection was tested using publicly available software tools, including 
      Breakdancer, ClusterFAST, CREST, and Hydra. Using Breakdancer and ClusterFAST, we 
      detected ALK rearrangements in seven of seven FISH-positive cases and KMT2A 
      rearrangements in six of six FISH-positive cases. Among the 77 ALK/KMT2A 
      FISH-negative cases, no false-positive identifications were made by Breakdancer 
      or ClusterFAST. Further, we identified one ALK rearranged case with a 
      noncanonical intron 16 breakpoint, which is likely to affect its response to 
      targeted inhibitors. We report that clinically relevant chromosomal 
      rearrangements can be detected from targeted gene panel-based next-generation 
      sequencing with sensitivity and specificity equivalent to that of FISH while 
      providing finer-scale information and increased efficiency for molecular oncology 
      testing.
CI  - Copyright (c) 2014 American Society for Investigative Pathology and the Association 
      for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
FAU - Abel, Haley J
AU  - Abel HJ
AD  - Department of Genetics, Washington University, St. Louis, Missouri.
FAU - Al-Kateb, Hussam
AU  - Al-Kateb H
AD  - Department of Pathology and Immunology, Washington University, St. Louis, 
      Missouri.
FAU - Cottrell, Catherine E
AU  - Cottrell CE
AD  - Department of Pathology and Immunology, Washington University, St. Louis, 
      Missouri.
FAU - Bredemeyer, Andrew J
AU  - Bredemeyer AJ
AD  - Department of Pathology and Immunology, Washington University, St. Louis, 
      Missouri.
FAU - Pritchard, Colin C
AU  - Pritchard CC
AD  - Department of Laboratory Medicine, University of Washington, Seattle, Washington.
FAU - Grossmann, Allie H
AU  - Grossmann AH
AD  - Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake 
      City, Utah.
FAU - Wallander, Michelle L
AU  - Wallander ML
AD  - ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah.
FAU - Pfeifer, John D
AU  - Pfeifer JD
AD  - Department of Pathology and Immunology, Washington University, St. Louis, 
      Missouri.
FAU - Lockwood, Christina M
AU  - Lockwood CM
AD  - Department of Pathology and Immunology, Washington University, St. Louis, 
      Missouri.
FAU - Duncavage, Eric J
AU  - Duncavage EJ
AD  - Department of Pathology and Immunology, Washington University, St. Louis, 
      Missouri. Electronic address: eduncavage@path.wustl.edu.
LA  - eng
GR  - K12 HL087107/HL/NHLBI NIH HHS/United States
GR  - K12HL087107-07/HL/NHLBI NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140509
PL  - United States
TA  - J Mol Diagn
JT  - The Journal of molecular diagnostics : JMD
JID - 100893612
RN  - 0 (KMT2A protein, human)
RN  - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adenocarcinoma/*genetics
MH  - Adenocarcinoma of Lung
MH  - Anaplastic Lymphoma Kinase
MH  - Carcinoma, Large Cell/*genetics
MH  - *Gene Rearrangement
MH  - High-Throughput Nucleotide Sequencing/*methods
MH  - Histone-Lysine N-Methyltransferase
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia/*genetics
MH  - Lung Neoplasms/*genetics
MH  - Myeloid-Lymphoid Leukemia Protein/*genetics
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Sensitivity and Specificity
PMC - PMC4078366
EDAT- 2014/05/13 06:00
MHDA- 2015/02/03 06:00
PMCR- 2015/07/01
CRDT- 2014/05/13 06:00
PHST- 2013/11/04 00:00 [received]
PHST- 2014/02/24 00:00 [revised]
PHST- 2014/03/06 00:00 [accepted]
PHST- 2014/05/13 06:00 [entrez]
PHST- 2014/05/13 06:00 [pubmed]
PHST- 2015/02/03 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - S1525-1578(14)00074-9 [pii]
AID - 10.1016/j.jmoldx.2014.03.006 [doi]
PST - ppublish
SO  - J Mol Diagn. 2014 Jul;16(4):405-17. doi: 10.1016/j.jmoldx.2014.03.006. Epub 2014 
      May 9.