PMID- 10416591
OWN - NLM
STAT- MEDLINE
DCOM- 19990812
LR  - 20220311
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 14
DP  - 1999 Jul 15
TI  - Beta-catenin mutations are specific for colorectal carcinomas with microsatellite
      instability but occur in endometrial carcinomas irrespective of mutator pathway.
PG  - 3346-51
AB  - Some colorectal tumors with wild-type adenomatous polyposis coli gene have
      activating mutations in beta-catenin (encoded by CTNNB1) that result in decreased
      phosphorylation by GSK-3beta and increased signaling through the Tcf/Lef
      transcription factors. To investigate the relationship between CTNNB1 mutations
      and underlying pathways of genomic instability, we examined 80 colorectal cancers
      stratified by the presence or absence of microsatellite instability (MSI). CTNNB1
      mutations were identified in 13 (25%) of 53 cancers with high frequency MSI
      (MSI-H), including 12 point mutations at exon 3 phosphorylation sites (codons 41 
      and 45) and one deletion of the entire exon 3 degradation box. No CTNNB1
      mutations were identified in 27 microsatellite stable or low frequency MSI
      (MSI-L) colorectal cancers (P < 0.01). In contrast, CTNNB1 mutations were
      identified in 3 of 9 (33%) MSI-H and 10 of 20 (50%) MSS/MSI-L endometrial
      carcinomas, suggesting a more generalized involvement in these tumors. Only six
      (46%) of the endometrial carcinoma CTNNB1 mutations occurred at residues directly
      phosphorylated by GSK-3beta, and only one of these was at either codon 41 or 45. 
      All point mutations in MSI-H cancers were transitions, whereas 64% of those in
      MSS/MSI-L cancers were transversions (P < 0.01). The differences in the mutation 
      profiles suggest that there may be molecular fingerprints of CTNNB1 mutations,
      determined by biological factors related to both tumor type and underlying
      pathways of genomic instability.
FAU - Mirabelli-Primdahl, L
AU  - Mirabelli-Primdahl L
AD  - Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai
      Hospital, Toronto, Ontario, Canada.
FAU - Gryfe, R
AU  - Gryfe R
FAU - Kim, H
AU  - Kim H
FAU - Millar, A
AU  - Millar A
FAU - Luceri, C
AU  - Luceri C
FAU - Dale, D
AU  - Dale D
FAU - Holowaty, E
AU  - Holowaty E
FAU - Bapat, B
AU  - Bapat B
FAU - Gallinger, S
AU  - Gallinger S
FAU - Redston, M
AU  - Redston M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Codon)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Adenocarcinoma/*genetics
MH  - Adenoma/genetics
MH  - Adenomatous Polyposis Coli/genetics
MH  - *Amino Acid Substitution
MH  - Cell Differentiation
MH  - Cell Transformation, Neoplastic/*genetics
MH  - Codon/genetics
MH  - Colonic Neoplasms/*genetics
MH  - Cytoskeletal Proteins/*genetics
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/genetics
MH  - Endometrial Neoplasms/*genetics
MH  - Exons/genetics
MH  - Female
MH  - Genes, APC
MH  - Humans
MH  - Male
MH  - *Microsatellite Repeats
MH  - Organ Specificity
MH  - Phosphorylation
MH  - *Point Mutation
MH  - Protein Processing, Post-Translational
MH  - Signal Transduction/genetics
MH  - *Trans-Activators
MH  - beta Catenin
EDAT- 1999/07/23 00:00
MHDA- 1999/07/23 00:01
CRDT- 1999/07/23 00:00
PHST- 1999/07/23 00:00 [pubmed]
PHST- 1999/07/23 00:01 [medline]
PHST- 1999/07/23 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Jul 15;59(14):3346-51.