Mismatch repair defects and Lynch syndrome: The role of the basic scientist in the battle against cancer

DNA Repair (Amst). 2016 Feb;38:127-134. doi: 10.1016/j.dnarep.2015.11.025. Epub 2015 Dec 2.


We have currently entered a genomic era of cancer research which may soon lead to a genomic era of cancer treatment. Patient DNA sequencing information may lead to a personalized approach to managing an individual's cancer as well as future cancer risk. The success of this approach, however, begins not necessarily in the clinician's office, but rather at the laboratory bench of the basic scientist. The basic scientist plays a critical role since the DNA sequencing information is of limited use unless one knows the function of the gene that is altered and the manner by which a sequence alteration affects that function. The role of basic science research in aiding the clinical management of a disease is perhaps best exemplified by considering the case of Lynch syndrome, a hereditary disease that predisposes patients to colorectal and other cancers. This review will examine how the diagnosis, treatment and even prevention of Lynch syndrome-associated cancers has benefitted from extensive basic science research on the DNA mismatch repair genes whose alteration underlies this condition.

Keywords: Chemotherapy; Colorectal cancer; Lynch syndrome; Microsatellite instability; Mismatch repair; Personalized medicine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis / drug therapy
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Mismatch Repair*
  • Genes, Neoplasm
  • Humans
  • Mutation / genetics