Heterozygous ATR mutations in mismatch repair-deficient cancer cells have functional significance.
Publication/Presentation Date
8-15-2005
Abstract
ATR (ataxia telangiectasia and Rad3-related) function is necessary for the proper response to commonly used chemotherapeutic agents. Heterozygous truncating mutations in exon 10 of the ATR gene have been described in numerous cancers exhibiting microsatellite instability. We show that truncating mutations of ATR are capable of acting in a dominant-negative manner to abrogate ATR-dependent Chk1 phosphorylation and cell-cycle arrests after DNA damage. In addition, endometrial cell lines harboring ATR mutations are defective for ATR-dependent responses. These findings imply that ATR mutations play an important role in the development and clinical behavior of a subset of microsatellite instability-positive endometrial, colon, and stomach cancers.
Volume
65
Issue
16
First Page
7091
Last Page
7095
ISSN
0008-5472
Published In/Presented At
Lewis, K. A., Mullany, S., Thomas, B., Chien, J., Loewen, R., Shridhar, V., & Cliby, W. A. (2005). Heterozygous ATR mutations in mismatch repair-deficient cancer cells have functional significance. Cancer research, 65(16), 7091–7095. https://doi.org/10.1158/0008-5472.CAN-05-1019
Disciplines
Medicine and Health Sciences
PubMedID
16103057
Department(s)
Department of Obstetrics and Gynecology
Document Type
Article