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Familial Cancer

, Volume 18, Issue 2, pp 173–178 | Cite as

Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma

  • P. Vande Perre
  • A. Siegfried
  • C. Corsini
  • D. Bonnet
  • C. Toulas
  • N. Hamzaoui
  • J. Selves
  • E. Chipoulet
  • J. S. Hoffmann
  • E. Uro-Coste
  • R. GuimbaudEmail author
Short Communication
  • 204 Downloads

Abstract

Germline mutations of the POLE gene are responsible for polymerase proofreading-associated polyposis syndrome (PPAP). These mutations were hypothesised to predispose to extra-gastrointestinal tumours (ovary, endometrium, brain), but this association has not been confirmed so far. We report a family with an autosomal dominant inheritance of PPAP due to a c.1089C>A; p.Asn363Lys mutation in the proofreading exonuclease domain of POLE. Ten patients presenting a history of colorectal tumours and three patients with polyposis are indexed in this family. Three carriers (including siblings and a distant cousin at 30, 45 and 52 respectively) and another member (at 37 not tested) presented glioblastoma. This is the second family reported to carry this mutation. Among the four glioblastomas in the family that we report, both show similar pathology: giant cell glioblastoma. These cases suggest that the c.1089C>A germline POLE mutation may confer an increased risk of brain cancer [incidence 17.4% (4/23) in mutation carriers combining the two families]. More observations are needed to support this hypothesis. It seems that not all mutations of POLE are equally associated with extra-gastrointestinal tumours. Although carriers of a mutation responsible for PPAP should benefit from screening for colorectal and uterine cancer, due to the rapid evolution of glioblastoma the value of neurological follow-up and brain imaging screening remains questionable. Nevertheless, considering the limitations of standard therapy for glioblastoma, mutation status could be useful for targeting therapy. The biological mechanism linking POLE mutation to glioblastoma remains to be determined.

Keywords

POLE Polymerase epsilon PPAP Proofreading Glioblastoma Giant cells 

Notes

Acknowledgements

We thank patients and patient families for their participation. We thank Doctor François Labrousse (CHU Limoges) for sharing histological data.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

Supplementary material

10689_2018_102_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 14 KB)

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Service de Génétique Médicale, Hôpital PurpanCHU de ToulouseToulouseFrance
  2. 2.Oncogénétique, Institut Claudius RegaudIUCT-OncopôleToulouseFrance
  3. 3.Université Toulouse III Paul SabatierToulouseFrance
  4. 4.Département de PathologieCHU de Toulouse, IUCT-OToulouseFrance
  5. 5.Service d’Oncogénétique, Département de Génétique MédicaleCHU de MontpellierMontpellierFrance
  6. 6.Oncologie Digestive: Pôle digestif- IUCT-Rangueil/LarreyCHU de ToulouseToulouseFrance
  7. 7.UMR 1037, CRCTToulouseFrance
  8. 8.Service de Biochimie et Génétique MoléculaireHôpital CochinParisFrance

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