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Nucleotide variants within the IQGAP1 gene in diffuse‐type gastric cancers
Author(s) -
Morris Leah E.,
Bloom George S.,
Frierson Henry F.,
Powell Steven M.
Publication year - 2005
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20150
Subject(s) - iqgap1 , biology , missense mutation , gene , cancer , cancer research , pathology , genetics , mutation , cell , medicine , cytoskeleton
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.