TY - JOUR
T1 - Searching for microsatellite mutations in coding regions in lung, breast, ovarian and colorectal cancers
AU - Forgacs, Eva
AU - Wren, Jonathan D.
AU - Kamibayashi, Craig
AU - Kondo, Masashi
AU - Xu, Xie L.
AU - Markowitz, Sanford
AU - Tomlinson, Gail E.
AU - Muller, Carolyn Y.
AU - Gazdar, Adi F.
AU - Garner, Harold R.
AU - Minna, John D.
N1 - Funding Information:
The authors thank James Lutterbaugh and Dr Donald Lombardi for tumor cell lines, and Luc Girard for helpful comments on this manuscript. This work has been supported by the National Cancer Institute Lung Cancer SPORE grant P50 CA70907, G Harold and Leila Y Mathers Charitable Foundation. HR Garner is supported by the Patrick O'Brien Montgomery Distinguished Chair. S Markowitz is an associate investigator of the Howard Hughes Medical Institute, and was also supported by PHS-CA 67409.
PY - 2001/2/22
Y1 - 2001/2/22
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/17744379148
UR - https://www.scopus.com/pages/publications/17744379148#tab=citedBy
U2 - 10.1038/sj.onc.1204211
DO - 10.1038/sj.onc.1204211
M3 - Article
C2 - 11314036
AN - SCOPUS:17744379148
SN - 0950-9232
VL - 20
SP - 1005
EP - 1009
JO - Oncogene
JF - Oncogene
IS - 8
ER -
