PMID- 31469468
OWN - NLM
STAT- MEDLINE
DCOM- 20200416
LR  - 20200416
IS  - 1098-2264 (Electronic)
IS  - 1045-2257 (Linking)
VI  - 59
IP  - 2
DP  - 2020 Feb
TI  - Detection of CSF1 rearrangements deleting the 3' UTR in tenosynovial giant cell 
      tumors.
PG  - 96-105
LID - 10.1002/gcc.22807 [doi]
AB  - Tenosynovial giant cell tumors (TGCTs) are characterized by rearrangements of 
      CSF1, thought to drive overexpression of macrophage colony-stimulating factor 
      (CSF1), thereby promoting tumor growth and recruitment of non-neoplastic 
      mononuclear and multinucleated inflammatory cells. While fusions to collagen 
      promoters have been described, the mechanism of CSF1 overexpression has been 
      unclear in a majority of cases. Two cohorts of TGCT were investigated for CSF1 
      rearrangements using fluorescence in situ hybridization (FISH) and either RNA-seq 
      or DNA-seq with Sanger validation. The study comprised 39 patients, including 13 
      localized TGCT, 21 diffuse TGCT, and five of unspecified type. CSF1 
      rearrangements were identified by FISH in 30 cases: 13 translocations, 17 3' 
      deletions. Sequencing confirmed CSF1 breakpoints in 28 cases; in all 28 the 
      breakpoint was found to be downstream of exon 5, replacing or deleting a long 3' 
      UTR containing known miRNA and AU-rich element negative regulatory sequences. We 
      also confirmed the presence of CBL exon 8-9 mutations in six of 21 cases. In 
      conclusion, TGCT in our large cohort were characterized by variable alterations, 
      all of which led to truncation of the 3' end of CSF1, instead of the COL6A3-CSF1 
      fusions previously reported in some TGCTs. The diversity of fusion partners but 
      consistent integrity of CSF1 functional domains encoded by exons 1-5 support a 
      hypothesis that CSF1 overexpression results from transcription of a truncated 
      form of CSF1 lacking 3' negative regulatory sequences. The presence of CBL 
      mutations affecting the linker and RING finger domain suggests an alternative 
      mechanism for increased CSF1/CSF1R signaling in some cases.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Ho, Julie
AU  - Ho J
AD  - Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, 
      British Columbia, Canada.
FAU - Peters, Thomas
AU  - Peters T
AD  - Novartis Institute for Biomedical Research, Basel, Switzerland.
FAU - Dickson, Brendan C
AU  - Dickson BC
AUID- ORCID: 0000-0003-2269-6216
AD  - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, 
      Ontario, Canada.
FAU - Swanson, David
AU  - Swanson D
AD  - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, 
      Ontario, Canada.
FAU - Fernandez, Anita
AU  - Fernandez A
AD  - Novartis Institute for Biomedical Research, Basel, Switzerland.
FAU - Frova-Seguin, Aurelie
AU  - Frova-Seguin A
AD  - Novartis Institute for Biomedical Research, Basel, Switzerland.
FAU - Valentin, Marie-Anne
AU  - Valentin MA
AD  - Novartis Institute for Biomedical Research, Basel, Switzerland.
FAU - Schramm, Ursula
AU  - Schramm U
AD  - Novartis Institute for Biomedical Research, Basel, Switzerland.
FAU - Sultan, Marc
AU  - Sultan M
AD  - Novartis Institute for Biomedical Research, Basel, Switzerland.
FAU - Nielsen, Torsten O
AU  - Nielsen TO
AD  - Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, 
      British Columbia, Canada.
FAU - Demicco, Elizabeth G
AU  - Demicco EG
AUID- ORCID: 0000-0003-4144-8824
AD  - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, 
      Ontario, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190912
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (3' Untranslated Regions)
RN  - 0 (CSF1 protein, human)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Adult
MH  - Aged
MH  - Cohort Studies
MH  - Exons
MH  - Female
MH  - Giant Cell Tumor of Tendon Sheath/diagnosis/*genetics/metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Macrophage Colony-Stimulating Factor/*genetics/metabolism
MH  - Male
MH  - Middle Aged
MH  - Translocation, Genetic
OTO - NOTNLM
OT  - 3' UTR
OT  - CBL
OT  - CSF1
OT  - pigmented villonodular synovitis
OT  - tenosynovial giant cell tumor
EDAT- 2019/08/31 06:00
MHDA- 2020/04/17 06:00
CRDT- 2019/08/31 06:00
PHST- 2019/07/17 00:00 [received]
PHST- 2019/08/25 00:00 [revised]
PHST- 2019/08/26 00:00 [accepted]
PHST- 2019/08/31 06:00 [pubmed]
PHST- 2020/04/17 06:00 [medline]
PHST- 2019/08/31 06:00 [entrez]
AID - 10.1002/gcc.22807 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2020 Feb;59(2):96-105. doi: 10.1002/gcc.22807. Epub 
      2019 Sep 12.