PMID- 10597266
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 47
DP  - 1999 Nov 11
TI  - Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic
      aggressive fibromatosis (desmoid tumor).
PG  - 6615-20
AB  - Aggressive fibromatosis (also called desmoid tumor) occurs as a sporadic lesion
      or as part of Familial Adenomatous Polyposis, which is caused by germ line
      mutations in the Adenomatous polyposis Coli (APC) gene. APC is involved in the
      regulation of the cellular level of beta-catenin, which is a mediator in Wnt
      signaling. Mutational analysis of the beta-catenin and APC genes was performed in
      42 sporadic aggressive fibromatoses. Nine tumors had mutations in APC, and 22 had
      a point mutation in beta-catenin at either codon 45 or codon 41 (producing a
      stabilized beta-catenin protein product). Immunohistochemistry showed an elevated
      beta-catenin protein level in all tumors, regardless of mutational status.
      Beta-catenin localized to the nucleus, and was not tyrosine phosphorylated in the
      six tumors in which this was tested. The demonstration of mutations in two
      mediators in the Wnt-APC-beta-catenin pathway implicates beta-catenin
      stabilization as the key factor in the pathogenesis of aggressive fibromatosis.
      This is the first demonstration of somatic beta-catenin mutations in a locally
      invasive, but non metastatic lesion composed of spindle cells, illustrating the
      importance of beta-catenin stabilization in a variety of cell types and
      neoplastic processes. Moreover, this tumor has one of the highest reported
      frequencies of beta-catenin mutations of any tumor type.
FAU - Tejpar, S
AU  - Tejpar S
AD  - Programme in Development Biology, Hospital for Sick Children, Toronto Ontario,
      Canada.
FAU - Nollet, F
AU  - Nollet F
FAU - Li, C
AU  - Li C
FAU - Wunder, J S
AU  - Wunder JS
FAU - Michils, G
AU  - Michils G
FAU - dal Cin, P
AU  - dal Cin P
FAU - Van Cutsem, E
AU  - Van Cutsem E
FAU - Bapat, B
AU  - Bapat B
FAU - van Roy, F
AU  - van Roy F
FAU - Cassiman, J J
AU  - Cassiman JJ
FAU - Alman, B A
AU  - Alman BA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
RN  - 42HK56048U (Tyrosine)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Base Sequence
MH  - Cytoskeletal Proteins/*genetics/metabolism
MH  - DNA
MH  - Fibroma/*genetics
MH  - *Gene Expression Regulation
MH  - *Genes, APC
MH  - Humans
MH  - *Mutation
MH  - Phosphorylation
MH  - *Trans-Activators
MH  - Tyrosine/metabolism
MH  - beta Catenin
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1038/sj.onc.1203041 [doi]
PST - ppublish
SO  - Oncogene. 1999 Nov 11;18(47):6615-20. doi: 10.1038/sj.onc.1203041.