@article{10cbbf498d184a7b8e12d618b5cd4906,
title = "Hypermutability and mismatch repair deficiency in RER+ tumor cells",
abstract = "A subset of sporadic colorectal tumors and most tumors developing in hereditary nonpolyposis colorectal cancer patients display frequent alterations in microsatellite sequences. Such tumors have been thought to manifest replication errors (RER+), but the basis for the alterations has remained conjectural. We demonstrate that the mutation rate of (CA)n repeats in RER+ tumor cells is at least 100-fold that in RER- tumor cells and show by in vitro assay that increased mutability of RER+ cells is associated with a profound defect in strand-specific mismatch repair. This deficiency was observed with microsatellite heteroduplexes as well as with heteroduplexes containing single base-base mismatches and affected an early step in the repair pathway. Thus, a true mutator phenotype exists in a subset of tumor cells, the responsible defect is likely to cause transitions and transversions in addition to microsatellite alterations, and a biochemical basis for this phenotype has been identified.",
author = "Ramon Parsons and Li, {Guo Min} and Longley, {Matthew J.} and Fang, {Woei horng} and Nickolas Papadopoulos and Jin Jen and {de la Chapelle}, Albert and Kinzler, {Kenneth W.} and Bert Vogelstein and Paul Modrich",
note = "Funding Information: Correspondence should be addressed to either B. V. or P. M. We gratefully acknowledge Ms. Sherry Larson and Ms. Alison Hayes of the Duke University Comprehensive Cancer Center Tissue Culture Facility for their expert assistance in growth of the cell lines used in the in vitro work. We also express our appreciation to Ms. Susanna Clark for her help in preparing nuclear extracts. This work was supported by grant GM45190 from the National Institute of General Medical Sciences (to P. M.); by grants CA35494 (to B. V.), CA09320 (to R. P.), CA09243 (to J. J.), and CA57345 (to K. W. K.) from the National Cancer Institute; by the American Cancer Society and the Clayton Fund (to 8. V.); by the Folkhaison Institute of Genetics, The Academy of Finland, and the Sigrid Juselius Foundation (to A. d. I. C.); and by American Cancer Society postdoctoral fellowship PF-3940 (to M. J. L.). G.-M. L. and M. J. L. contributed equally to the biochemical work, as did R. P. and N. P. to the genetic studies described herein.",
year = "1993",
month = dec,
day = "17",
doi = "10.1016/0092-8674(93)90331-J",
language = "English",
volume = "75",
pages = "1227--1236",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",
}