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[Cancer Research 59, 4213-4215, September 1, 1999]
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[Cancer Research 59, 4213-4215, September 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Frequent Frameshift Mutations of the TCF-4 Gene in Colorectal Cancers with Microsatellite Instability1

Alex Duval, Jacqueline Gayet, Xiao-Ping Zhou, Barry Iacopetta, Gilles Thomas and Richard Hamelin2

INSERM U434-Centre d’Etude de Polymorphisme Humane, 75010 Paris, France [A. D., J. G., X-P. Z., G. T., R. H.], and Department of Surgery, University of Western Australia, Nedlands, 6907 Australia [B. I.]

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 TGFß-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 coli (APC)/ß-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.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.