PMS2 monoallelic mutation carriers: the known unknown. Review uri icon

Overview

MeSH

  • Early Detection of Cancer
  • Germ-Line Mutation
  • Heterozygote
  • Humans
  • Mismatch Repair Endonuclease PMS2
  • Penetrance

MeSH Major

  • Adenosine Triphosphatases
  • Colorectal Neoplasms, Hereditary Nonpolyposis
  • DNA Repair Enzymes
  • DNA-Binding Proteins

abstract

  • Germ-line mutations in MLH1, MSH2, MSH6, and PMS2 have been shown to cause Lynch syndrome. The penetrance of the cancer and tumor spectrum has been repeatedly studied, and multiple professional societies have proposed clinical management guidelines for affected individuals. Several studies have demonstrated a reduced penetrance for monoallelic carriers of PMS2 mutations compared with the other mismatch repair (MMR) genes, but clinical management guidelines have largely proposed the same screening recommendations for all MMR gene carriers. The authors considered whether enough evidence existed to propose new screening guidelines specific to PMS2 mutation carriers with regard to age at onset and frequency of colonic screening. Published reports of PMS2 germ-line mutations were combined with unpublished cases from the authors' research registries and clinical practices, and a discussion of potential modification of cancer screening guidelines was pursued. A total of 234 monoallelic PMS2 mutation carriers from 170 families were included. Approximately 8% of those with colorectal cancer (CRC) were diagnosed before age 30, and each of these tumors presented on the left side of the colon. As it is currently unknown what causes the early onset of CRC in some families with monoallelic PMS2 germline mutations, the authors recommend against reducing cancer surveillance guidelines in families found having monoallelic PMS2 mutations in spite of the reduced penetrance.Genet Med 18 1, 13-19.

authors

publication date

  • January 2016

has subject area

  • Adenosine Triphosphatases
  • Colorectal Neoplasms, Hereditary Nonpolyposis
  • DNA Repair Enzymes
  • DNA-Binding Proteins
  • Early Detection of Cancer
  • Germ-Line Mutation
  • Heterozygote
  • Humans
  • Mismatch Repair Endonuclease PMS2
  • Penetrance

Research

keywords

  • Journal Article
  • Review

Identity

Language

  • eng

PubMed Central ID

  • PMC4834863

Digital Object Identifier (DOI)

  • 10.1038/gim.2015.27

PubMed ID

  • 25856668

Additional Document Info

start page

  • 13

end page

  • 19

volume

  • 18

number

  • 1