PMID- 10197610
OWN - NLM
STAT- MEDLINE
DCOM- 19990421
LR  - 20071114
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 7
DP  - 1999 Apr 1
TI  - Beta-catenin mutations are more frequent in small colorectal adenomas than in
      larger adenomas and invasive carcinomas.
PG  - 1442-4
AB  - Loss of serine or threonine phosphorylation sites from exon 3 of beta-catenin has
      been identified in approximately half of colorectal tumors which lack adenomatous
      polyposis coli (APC) mutations, but the overall contribution of beta-catenin
      mutations to sporadic colorectal tumorigenesis is unclear. We therefore used PCR 
      to amplify and sequence exon 3 of beta-catenin from 202 sporadic colorectal
      tumors. Exon 3 beta-catenin mutations were identified in 6 of 48 small (< 1 cm)
      adenomas, 2 of 82 large (> or =1 cm) adenomas, and 1 of 72 invasive carcinomas.
      Eight of the nine mutations, including all of those in the small adenomas and the
      invasive cancer, involved loss of serine or threonine phosphorylation sites. The 
      percentage of beta-catenin mutations in small adenomas (12.5%) was significantly 
      greater than that in large adenomas (2.4%) and invasive cancers (1.4%; P = 0.05
      and P = 0.02, respectively). We conclude that mutation of beta-catenin can be an 
      early, perhaps initiating, event in colorectal tumorigenesis. Small adenomas with
      beta-catenin mutations do not appear to be as likely to progress to larger
      adenomas and invasive carcinomas as other adenomas, however, with the result that
      beta-catenin mutations are only rarely seen in invasive cancers. This suggests
      that APC and beta-catenin mutations are not functionally equivalent, and that the
      APC gene may have other tumor suppressor functions besides the degradation of
      beta-catenin.
FAU - Samowitz, W S
AU  - Samowitz WS
AD  - Department of Pathology, University of Utah Health Sciences Center, Salt Lake
      City 84132, USA.
FAU - Powers, M D
AU  - Powers MD
FAU - Spirio, L N
AU  - Spirio LN
FAU - Nollet, F
AU  - Nollet F
FAU - van Roy, F
AU  - van Roy F
FAU - Slattery, M L
AU  - Slattery ML
LA  - eng
GR  - CA01755/CA/NCI NIH HHS/United States
GR  - CA48998/CA/NCI NIH HHS/United States
GR  - CA61757/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Adenoma/*genetics
MH  - Aged
MH  - Colorectal Neoplasms/*genetics
MH  - Cytoskeletal Proteins/*genetics
MH  - Genes, APC
MH  - Humans
MH  - Middle Aged
MH  - *Mutation
MH  - *Trans-Activators
MH  - beta Catenin
EDAT- 1999/04/10 00:00
MHDA- 1999/04/10 00:01
CRDT- 1999/04/10 00:00
PHST- 1999/04/10 00:00 [pubmed]
PHST- 1999/04/10 00:01 [medline]
PHST- 1999/04/10 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Apr 1;59(7):1442-4.