Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome

Eur J Neurol. 2015 Apr;22(4):717-24. doi: 10.1111/ene.12647. Epub 2015 Jan 19.


Background and purpose: Brain tumors represent a rare and relatively uncharacterized tumor type in Lynch syndrome.

Methods: The national Danish Hereditary Nonpolyposis Colorectal Cancer Register was utilized to estimate the cumulative life-time risk for brain tumors in Lynch syndrome, and the mismatch repair (MMR) status in all tumors available was evaluated.

Results: Primary brain tumors developed in 41/288 families at a median age of 41.5 (range 2-73) years. Biallelic MMR gene mutations were linked to brain tumor development in childhood. The risk of brain tumors was significantly higher (2.5%) in MSH2 gene mutation carriers compared to patients with mutations in MLH1 or MSH6. Glioblastomas predominated (56%), followed by astrocytomas (22%) and oligodendrogliomas (9%). MMR status was assessed in 10 tumors, eight of which showed MMR defects. None of these tumors showed immunohistochemical staining suggestive of the IDH1 R132H mutation.

Conclusion: In Lynch syndrome brain tumors occurred in 14% of the families with significantly higher risks for individuals with MSH2 gene mutations and development of childhood brain tumors in individuals with constitutional MMR defects.

Keywords: IDH1; Muir-Torre syndrome; Turcot's syndrome; cumulative incidence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Astrocytoma / epidemiology*
  • Child
  • Child, Preschool
  • Colorectal Neoplasms, Hereditary Nonpolyposis / epidemiology*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Comorbidity
  • Denmark / epidemiology
  • Female
  • Glioblastoma / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Oligodendroglioma / epidemiology*
  • Registries*
  • Young Adult