Concurrent genetic alterations in DNA polymerase proofreading and mismatch repair in human colorectal cancer.

ABSTRACT: Genomic sequences encoding the 3' exonuclease (proofreading) domains of both replicative DNA polymerases, pol delta and pol epsilon, were explored simultaneously in human colorectal carcinomas including six established cell lines. Three unequivocal sequence alterations, including one previously reported, were found, and all these were considered as dysfunctional mutations in light of the local amino-acid sequences. In particular, the F367S mutation found in the POLE gene encoding the pol epsilon catalytic subunit, which includes the proofreading domain, is the first found in human diseases. Surprisingly, the tumours carrying these proofreading domain mutations were all defective in DNA mismatch repair (MMR). In addition to the two cell lines with acknowledged MMR gene mutations, the third

SUBMITTER: Yoshida R 

PROVIDER: S-EPMC3061989 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature