Ontology type: schema:ScholarlyArticle Open Access: True
2001-02-22
AUTHORSEva Forgacs, Jonathan D Wren, Craig Kamibayashi, Masashi Kondo, Xie L Xu, Sanford Markowitz, Gail E Tomlinson, Carolyn Y Muller, Adi F Gazdar, Harold R Garner, John D Minna
ABSTRACTRepX represents a new informatics approach to probe the UniGene database for potentially polymorphic repeat sequences in the open reading frame (ORF) of genes, 56% of which were found to be actually polymorphic. We now have performed mutational analysis of 17 such sites in genes not found to be polymorphic (<0.03 frequency) in a large panel of human cancer genomic DNAs derived from 31 lung, 21 breast, seven ovarian, 21 (13 microsatellite instability (MSI)+ and eight MSI−) colorectal cancer cell lines. In the lung, breast and ovarian tumor DNAs we found no mutations (<0.03–0.04 rate of tumor associated open reading frame mutations) in these sequences. By contrast, 18 MSI+ colorectal cancers (13 cancer cell lines and five primary tumors) with mismatch repair defects exhibited six mutations in three of the 17 genes (SREBP-2, TAN-1, GR6) (P<0.000003 compared to all other cancers tested). We conclude that coding region microsatellite alterations are rare in lung, breast, ovarian carcinomas and MSI (−) colorectal cancers, but are relatively frequent in MSI (+) colorectal cancers with mismatch repair deficits. More... »
PAGES1005-1009
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DOIhttp://dx.doi.org/10.1038/sj.onc.1204211
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