Searching for microsatellite mutations in coding regions in lung, breast, ovarian and colorectal cancers

Eva 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

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16 Scopus citations

Abstract

RepX 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.

Original languageEnglish (US)
Pages (from-to)1005-1009
Number of pages5
JournalOncogene
Volume20
Issue number8
DOIs
StatePublished - Feb 22 2001

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Keywords

  • Microsatellite instability
  • Mutation
  • Repetitive DNA sequences

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Forgacs, E., Wren, J. D., Kamibayashi, C., Kondo, M., Xu, X. L., Markowitz, S., Tomlinson, G. E., Muller, C. Y., Gazdar, A. F., Garner, H. R., & Minna, J. D. (2001). Searching for microsatellite mutations in coding regions in lung, breast, ovarian and colorectal cancers. Oncogene, 20(8), 1005-1009. https://doi.org/10.1038/sj.onc.1204211