Increased Transversions in a Novel Mutator Colon Cancer Cell Line
Oncogene (1998) 16, 1125 ± 1130 1998 Stockton Press All rights reserved 0950 ± 9232/98 $12.00 Increased transversions in a novel mutator colon cancer cell line James R Eshleman1,6, P Scott Donover2, Susan J Littman5, Sandra E Swinler2, Guo-Min Li4,7, James D Lutterbaugh2, James KV Willson2, Paul Modrich4, W David Sedwick2, Sanford D Markowitz2 and Martina L Veigl3 1Departments of Pathology; 2Medicine; 3General Medical Sciences and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University, Suite 200, UCRC II, 11001 Cedar Road, Cleveland, Ohio 44106; 4Department of Biochemistry and Howard Hughes Medical Institute; 5Department of Medicine-Oncology, Duke University Medical Center, Nanaline Duke Building, Durham, North Carolina, 27710 USA We describe a novel mutator phenotype in the Vaco411 In this report we describe the unique speci®city of a colon cancer cell line which increases the spontaneous new mutator defect, which is independent of MMR. mutation rate 10 ± 100-fold over background. This We have previously shown that the Vaco411 colon mutator results primarily in transversion base substitu- cancer cell line displays a moderately (10 ± 100-fold) tions which are found infrequently in repair competent increased spontaneous mutation rate (Eshleman et al., cells. Of the four possible types of transversions, only 1995), and does not exhibit the RER phenotype which three were principally recovered. Spontaneous mutations generally accompanies MMR defects (Eshleman and recovered also included transitions and large deletions, Markowitz, 1995). We now describe the spontaneous but very few frameshifts were recovered. When compared hprt mutations arising in this new colon cancer to known mismatch repair defective colon cancer mutator, and compare these mutations to the repair mutators, the distribution of mutations in Vaco411 is capacity exhibited by cell-free extracts of this cell line.
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