Alterations of the double-strand break repair gene MRE11 in cancer

MRE11 plays a role in DNA double-strand break repair. Hypomorphic mutations of MRE11 have been demonstrated in ataxia-telangiectasia (AT)-like disorde r. ATM mutations play a causal role in AT and have been demonstrated in lym phoid malignancies in patients without AT histories. By analogy with the re lationship of ATM to lymphoid malignancies, it is probable that alterations of MRE11 are associated with tumor formation. We performed a mutation anal ysis of MRE11 in 159 unselected primary tumors. Three missense mutations at conserved positions were found in breast and lymphoid tumors. Additionally , an aberrant transcript without genomic mutation was found in a breast tum or. These findings suggest an occasional role for MRE11 alterations in the development of primary tumors.