PMID- 10485457
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20101118
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 17
DP  - 1999 Sep 1
TI  - Frequent frameshift mutations of the TCF-4 gene in colorectal cancers with
      microsatellite instability.
PG  - 4213-5
AB  - About 15% of sporadic colorectal cancers show microsatellite instability (MSI)
      due to the inactivation of mismatch repair genes and are termed MSI-H tumors. In 
      these tumors, frameshift mutations in coding repeats have been found within the
      TGFbeta-RII, BAX, and IGFRII genes that are probably involved in their
      progression. In the present work, we report frequent mutations in TCF-4, another 
      target gene for instability. TCF-4 codes for a transcription factor that is a
      crucial member of the adenomatous polyposis coil (APC)/beta-catenin/T-cell factor
      (TCF) pathway. Fifty percent (4 of 8) of human MSI-H colorectal cell lines and
      39% (19 of 49) of MSI-H colorectal primary tumors were found to have a 1-bp
      deletion in an (A)9 repeat within the coding region of this gene. In contrast, a 
      frameshift mutation was found in only 1 of 56 non-MSI colorectal tumors and in
      none of 16 non-MSI colorectal cancer cell lines. These results suggest that TCF-4
      frameshift mutations are selected for and play a role in colorectal MSI-H
      tumorigenesis. Depending on different reading frames due to alternatively spliced
      TCF-4 mRNA, the (A)9 repeat normally codes for several isoforms that could serve 
      as modulators of TCF-4 transcriptional activity. The deletion of one nucleotide
      in this repeat could change TCF-4 transactivating properties by modifying the
      respective proportions of the different isoforms.
FAU - Duval, A
AU  - Duval A
AD  - INSERM U434-Centre d'Etude de Polymorphisme Humane, Paris, France.
FAU - Gayet, J
AU  - Gayet J
FAU - Zhou, X P
AU  - Zhou XP
FAU - Iacopetta, B
AU  - Iacopetta B
FAU - Thomas, G
AU  - Thomas G
FAU - Hamelin, R
AU  - Hamelin R
LA  - eng
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 (Cytoskeletal Proteins)
RN  - 0 (TCF Transcription Factors)
RN  - 0 (TCF7L2 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factor 7-Like 2 Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Colorectal Neoplasms/*genetics
MH  - Cytoskeletal Proteins/genetics
MH  - *Frameshift Mutation
MH  - Genes, APC
MH  - Humans
MH  - *Microsatellite Repeats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - TCF Transcription Factors
MH  - *Trans-Activators
MH  - Transcription Factor 7-Like 2 Protein
MH  - Transcription Factors/*genetics
MH  - Tumor Cells, Cultured
MH  - beta Catenin
EDAT- 1999/09/15 00:00
MHDA- 1999/09/15 00:01
CRDT- 1999/09/15 00:00
PHST- 1999/09/15 00:00 [pubmed]
PHST- 1999/09/15 00:01 [medline]
PHST- 1999/09/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Sep 1;59(17):4213-5.