PMID- 26572152
OWN - NLM
STAT- MEDLINE
DCOM- 20170201
LR  - 20181113
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 37
IP  - 4
DP  - 2016 Apr
TI  - Identification of CTNNB1 mutations, CTNNB1 amplifications, and an Axin2 splice 
      variant in juvenile angiofibromas.
PG  - 5539-49
LID - 10.1007/s13277-015-4422-y [doi]
AB  - Juvenile angiofibromas (JAs) are benign fibro-vascular tumors occurring nearly 
      exclusively in adolescent males. Even less is known about this rare tumor entity, 
      alterations affecting the Wnt-pathway seem to play a pivotal role in tumor 
      biology as activating CTNNB1 mutations have been detected. However, the knowledge 
      of Wnt-pathway changes is still limited. Therefore, we aimed to determine in JAs 
      further insight into Wnt/beta-catenin pathway components. In our present study, 
      genetic alterations of the Wnt-pathway members CTNNB1, APC, GSK3beta, and Axin2 
      detected by metaphase comparative genomic hybridization (CGH) were shown to 
      result in elevated transcript levels in the majority of JA samples compared to 
      nasal mucosa stroma (p < 0.001, p = 0.001, p = 0.046, and p = 0.006, 
      respectively). Additionally, amplifications of CTNNB1 were validated by 
      fluorescence in situ hybridization (FISH) and genomic qPCR. Moreover, our 
      mutation analysis detected already known mutations as well as, to the best of our 
      knowledge, mutations and an interstitial deletion of CTNNB1 not described in JAs 
      before. Additionally, a so far unknown transcribed Axin2 splice variant was 
      found, but no further Axin2 mutations. Taken together, our current study supports 
      the importance of aberrant Wnt-signaling as a common event in JAs, most likely by 
      the observed genetic alterations driven by mutations, interstitial deletions but 
      also amplifications of CTNNB1 contributing to the stabilization of beta-catenin.
FAU - Wemmert, Silke
AU  - Wemmert S
AD  - Department of Otolaryngology, Saarland University Medical Center, 66421, 
      Homburg/Saar, Germany. silke.wemmert@uks.eu.
FAU - Willnecker, Vivienne
AU  - Willnecker V
AD  - Department of Otolaryngology, Saarland University Medical Center, 66421, 
      Homburg/Saar, Germany.
FAU - Kulas, Philipp
AU  - Kulas P
AD  - Department of Otolaryngology, Saarland University Medical Center, 66421, 
      Homburg/Saar, Germany.
FAU - Weber, Stefanie
AU  - Weber S
AD  - Department of Otolaryngology, Saarland University Medical Center, 66421, 
      Homburg/Saar, Germany.
FAU - Lerner, Cornelia
AU  - Lerner C
AD  - Department of Otolaryngology, Saarland University Medical Center, 66421, 
      Homburg/Saar, Germany.
FAU - Berndt, Sabrina
AU  - Berndt S
AD  - Department of Otolaryngology, Saarland University Medical Center, 66421, 
      Homburg/Saar, Germany.
FAU - Wendler, Olaf
AU  - Wendler O
AD  - Experimental Otorhinolaryngology, ENT-Hospital, Head and Neck Surgery, 
      Friedrich-Alexander University Erlangen-Nurnberg (FAU), Erlangen, 91054, Germany.
FAU - Schick, Bernhard
AU  - Schick B
AD  - Department of Otolaryngology, Saarland University Medical Center, 66421, 
      Homburg/Saar, Germany.
LA  - eng
PT  - Journal Article
DEP - 20151117
PL  - Netherlands
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental 
      Biology and Medicine
JID - 8409922
RN  - 0 (APC protein, human)
RN  - 0 (AXIN2 protein, human)
RN  - 0 (Adenomatous Polyposis Coli Protein)
RN  - 0 (Axin Protein)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Protein Isoforms)
RN  - 0 (beta Catenin)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
SB  - IM
MH  - Adenomatous Polyposis Coli Protein/genetics
MH  - Adolescent
MH  - Adult
MH  - Angiofibroma/*genetics/pathology
MH  - Axin Protein/*genetics
MH  - Child
MH  - Glycogen Synthase Kinase 3 beta/genetics
MH  - Humans
MH  - Male
MH  - Mutation
MH  - Protein Isoforms/*genetics
MH  - Wnt Signaling Pathway/genetics
MH  - Young Adult
MH  - beta Catenin/*genetics
OTO - NOTNLM
OT  - FISH
OT  - Juvenile angiofibroma
OT  - Mutations
OT  - qPCR
OT  - beta-Catenin
EDAT- 2015/11/18 06:00
MHDA- 2017/02/02 06:00
CRDT- 2015/11/18 06:00
PHST- 2015/08/17 00:00 [received]
PHST- 2015/11/10 00:00 [accepted]
PHST- 2015/11/18 06:00 [entrez]
PHST- 2015/11/18 06:00 [pubmed]
PHST- 2017/02/02 06:00 [medline]
AID - 10.1007/s13277-015-4422-y [pii]
AID - 10.1007/s13277-015-4422-y [doi]
PST - ppublish
SO  - Tumour Biol. 2016 Apr;37(4):5539-49. doi: 10.1007/s13277-015-4422-y. Epub 2015 
      Nov 17.