Colon Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Colon Cancer, including details on causes, treatment, symptoms.

Heterozygous ATR mutations in mismatch repair-deficient cancer cells have functional significance.

Lewis KA, Mullany S, Thomas B, Chien J, Loewen R, Shridhar V, Cliby WA

Department of Obstetrics and Gynecology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.

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.

Published 16 August 2005 in Cancer Res, 65(16): 7091-5.
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