Polymerase proofreading-associated polyposis: a new, dominantly inherited syndrome of hereditary colorectal cancer predisposition

Dis Colon Rectum. 2014 Mar;57(3):396-7. doi: 10.1097/DCR.0000000000000084.


Germline mutations in the exonuclease (proofreading) domains of 2 DNA polymerases (POLE and POLD1) have been associated with a dominantly inherited, highly penetrant syndrome of oligo adenomatous polyposis and early-age-of-diagnosis colorectal cancer and endometrial cancer. The loss of proofreading capability causes multiple mutations throughout the genome and is manifest as microsatellite-stable, chromosomal unstable cancers. This is an important addition to the range of dominantly inherited syndromes of colorectal cancer predisposition.

MeSH terms

  • Adenomatous Polyposis Coli / genetics*
  • Colorectal Neoplasms / genetics*
  • DNA Mismatch Repair / genetics
  • DNA Polymerase II / genetics*
  • DNA Polymerase III / genetics*
  • DNA Replication / genetics
  • Exodeoxyribonucleases / genetics
  • Genetic Predisposition to Disease*
  • Genotype
  • Germ-Line Mutation / genetics
  • Humans
  • Phenotype
  • Poly-ADP-Ribose Binding Proteins
  • Syndrome


  • Poly-ADP-Ribose Binding Proteins
  • POLD1 protein, human
  • DNA Polymerase II
  • DNA Polymerase III
  • POLE protein, human
  • Exodeoxyribonucleases