PMID- 23761323
OWN - NLM
STAT- MEDLINE
DCOM- 20140204
LR  - 20130828
IS  - 1098-2264 (Electronic)
IS  - 1045-2257 (Linking)
VI  - 52
IP  - 10
DP  - 2013 Oct
TI  - Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, 
      nonrandom secondary genomic imbalances, and a characteristic gene expression 
      profile in solitary fibrous tumor.
PG  - 873-86
LID - 10.1002/gcc.22083 [doi]
AB  - Solitary fibrous tumor (SFT) is a mesenchymal neoplasm displaying variable 
      morphologic and clinical features. To identify pathogenetically important genetic 
      rearrangements, 44 SFTs were analyzed using a variety of techniques. Chromosome 
      banding and fluorescence in situ hybridization (FISH) showed recurrent 
      breakpoints in 12q13, clustering near the NAB2 and STAT6 genes, and single 
      nucleotide polymorphism array analysis disclosed frequent deletions affecting 
      STAT6. Quantitative real-time PCR revealed high expression levels of the 5'-end 
      of NAB2 and the 3'-end of STAT6, which at deep sequencing of enriched DNA 
      corresponded to NAB2/STAT6 fusions. Subsequent reverse-transcriptase PCR (RT-PCR) 
      analysis identified a NAB2/STAT6 fusion in 37/41 cases, confirming that this 
      fusion gene underlies the pathogenesis of SFT. The hypothesis that the NAB2/STAT6 
      fusions will result in altered properties of the transcriptional co-repressor 
      NAB2--a key regulator of the early growth response 1 (EGR1) transcription factor 
      - was corroborated by global gene expression analysis; SFTs showed deregulated 
      expression of EGR1 target genes, as well as of other, developmentally important 
      genes. We also identified several nonrandom secondary changes, notably loss of 
      material from 13q and 14q. As neither chromosome banding nor FISH analysis 
      identify more than a minor fraction of the fusion-positive cases, and because 
      multiple primer combinations are required to identify all possible fusion 
      transcripts by RT-PCR, alternative diagnostic markers might instead be found 
      among deregulated genes identified at global gene expression analysis. Indeed, 
      using immunohistochemistry on tissue microarrays, the top up-regulated gene, 
      GRIA2, was found to be differentially expressed also at the protein level.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Mohajeri, Arezoo
AU  - Mohajeri A
AD  - Department of Clinical Genetics, University and Regional Laboratories, Lund 
      University, Lund, Sweden.
FAU - Tayebwa, Johnbosco
AU  - Tayebwa J
FAU - Collin, Anna
AU  - Collin A
FAU - Nilsson, Jenny
AU  - Nilsson J
FAU - Magnusson, Linda
AU  - Magnusson L
FAU - von Steyern, Fredrik Vult
AU  - von Steyern FV
FAU - Brosjo, Otte
AU  - Brosjo O
FAU - Domanski, Henryk A
AU  - Domanski HA
FAU - Larsson, Olle
AU  - Larsson O
FAU - Sciot, Raf
AU  - Sciot R
FAU - Debiec-Rychter, Maria
AU  - Debiec-Rychter M
FAU - Hornick, Jason L
AU  - Hornick JL
FAU - Mandahl, Nils
AU  - Mandahl N
FAU - Nord, Karolin H
AU  - Nord KH
FAU - Mertens, Fredrik
AU  - Mertens F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130612
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (NAB2 protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Repressor Proteins)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (STAT6 protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single Nucleotide
MH  - Repressor Proteins/*genetics
MH  - STAT6 Transcription Factor/*genetics
MH  - Solitary Fibrous Tumors/*genetics
MH  - Transcriptome
MH  - Young Adult
OTO - NOTNLM
OT  - The Swedish Cancer Foundation
OT  - and the Medical Faculty of Lund University
OT  - the Gunnar Nilsson Cancer Foundation
OT  - the IngaBritt and Arne Lundberg Foundation
OT  - the National Research Council of Sweden
OT  - the Swedish Childhood Cancer Foundation
EDAT- 2013/06/14 06:00
MHDA- 2014/02/05 06:00
CRDT- 2013/06/14 06:00
PHST- 2013/05/14 00:00 [received]
PHST- 2013/05/14 00:00 [revised]
PHST- 2013/05/16 00:00 [accepted]
PHST- 2013/06/14 06:00 [entrez]
PHST- 2013/06/14 06:00 [pubmed]
PHST- 2014/02/05 06:00 [medline]
AID - 10.1002/gcc.22083 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2013 Oct;52(10):873-86. doi: 10.1002/gcc.22083. Epub 
      2013 Jun 12.