Nucleotide variants within the IQGAP1 gene in diffuse-type gastric cancers

IQGAP1 is recognized as a negative regulator of cell–cell adhesion at adherens junctions in several cell types, including gastric mucosal cells. The histopathologic appearance of diffuse gastric carcinoma is defined by non‐ or poorly cohesive tumor cells, indicating abnormal intercellular adhesion....

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Published in:Genes chromosomes & cancer 2005-03, Vol.42 (3), p.280-286
Main Authors: Morris, Leah E., Bloom, George S., Frierson Jr, Henry F., Powell, Steven M.
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Animals
Genetic Variation
Humans
Intestinal Neoplasms - genetics
Intestinal Neoplasms - metabolism
Intestinal Neoplasms - pathology
Introns - genetics
Mice
Mice, SCID
Mutation - genetics
ras GTPase-Activating Proteins - genetics
ras GTPase-Activating Proteins - metabolism
Stomach - metabolism
Stomach - pathology
Stomach Neoplasms - genetics
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Transplantation, Heterologous
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Summary:IQGAP1 is recognized as a negative regulator of cell–cell adhesion at adherens junctions in several cell types, including gastric mucosal cells. The histopathologic appearance of diffuse gastric carcinoma is defined by non‐ or poorly cohesive tumor cells, indicating abnormal intercellular adhesion. Hence, we screened 38 gastric cancers for activating point mutations in IQGAP1. In 2 of the 33 diffuse gastric cancers, there was a missense nucleotide change predicted to alter the amino acid sequence in the GAP‐related domain, which includes part of the binding site for the activated small G proteins Cdc42 and Rac1. Many intronic IQGAP1 gene changes were observed, and several occurred more frequently in diffuse‐type gastric cancers than in intestinal‐type gastric cancers. A highly variable pentanucleotide repeat was identified in the final intron of IQGAP1. The most expanded six‐repeat sequence was present exclusively in diffuse‐type gastric cancers. Additionally, 19 diffuse cases and two intestinal cases exhibited silent coding region nucleotide alterations. Taken together, our results suggest that IQGAP1 coding sequence mutations are not a frequent event in gastric cancer, but do occur in a subset of diffuse‐type gastric carcinomas. Additional studies analyzing other proteins involved in cell adhesion may lead to a better molecular understanding of the histopathologic appearance of diffuse gastric cancers. © 2004 Wiley‐Liss, Inc.
ISSN:1045-2257
1098-2264
DOI:10.1002/gcc.20150