Human Genetics

, Volume 135, Issue 5, pp 469–475 | Cite as

No correlation between NF1 mutation position and risk of optic pathway glioma in 77 unrelated NF1 patients

  • Sonja Hutter
  • Rosario M. Piro
  • Sebastian M. Waszak
  • Hildegard Kehrer-Sawatzki
  • Reinhard E. Friedrich
  • Alvaro Lassaletta
  • Olaf Witt
  • Jan O. Korbel
  • Peter Lichter
  • Martin U. Schuhmann
  • Stefan M. Pfister
  • Uri Tabori
  • Victor F. Mautner
  • David T. W. Jones
Original Investigation

Abstract

Neurofibromatosis type 1 (NF1) is a common monogenic disorder whereby affected individuals are predisposed to developing CNS tumors, including optic pathway gliomas (OPGs, occurring in ~15 to 20 % of cases). So far, no definite genotype–phenotype correlation determining NF1 patients at risk for tumor formation has been described, although enrichment for mutations in the 5′ region of the NF1 gene in OPG patients has been suggested. We used whole exome sequencing, targeted sequencing, and copy number analysis to screen 77 unrelated NF1 patients with (n = 41) or without (n = 36; age ≥10 years) optic pathway glioma for germline NF1 alterations. We identified germline NF1 mutations in 69 of 77 patients (90 %), but no genotype–phenotype correlation was observed. Our data using a larger patient cohort did not confirm the previously reported clustering of mutations in the 5′ region of the NF1 gene in patients with OPG. Thus, NF1 mutation location should not currently be used as a clinical criterion to assess the risk of developing OPGs.

Supplementary material

439_2016_1646_MOESM1_ESM.docx (6.7 mb)
Supplementary material 1 (DOCX 6895 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Sonja Hutter
    • 1
  • Rosario M. Piro
    • 2
    • 3
    • 4
    • 5
  • Sebastian M. Waszak
    • 6
  • Hildegard Kehrer-Sawatzki
    • 7
  • Reinhard E. Friedrich
    • 8
  • Alvaro Lassaletta
    • 9
  • Olaf Witt
    • 3
    • 10
    • 11
    • 12
  • Jan O. Korbel
    • 6
  • Peter Lichter
    • 2
    • 3
  • Martin U. Schuhmann
    • 13
    • 14
    • 15
  • Stefan M. Pfister
    • 1
    • 3
    • 11
    • 12
  • Uri Tabori
    • 9
  • Victor F. Mautner
    • 16
  • David T. W. Jones
    • 1
    • 3
  1. 1.Division of Pediatric NeurooncologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.Division of Molecular GeneticsGerman Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.German Cancer Consortium (DKTK) Core Center HeidelbergHeidelbergGermany
  4. 4.Institute of Computer ScienceFreie Universität BerlinBerlinGermany
  5. 5.Institute of Medical Genetics and Human Genetics, Charité University HospitalBerlinGermany
  6. 6.European Molecular Biology Laboratory (EMBL), Genome Biology Research UnitHeidelbergGermany
  7. 7.Institute of Human GeneticsUniversity of UlmUlmGermany
  8. 8.Department of Oral and Cranio-Maxillofacial SurgeryUniversity Hospital Hamburg-EppendorfHamburgGermany
  9. 9.Division of Hematology/Oncology, Department of PediatricsHospital for Sick Children, University of TorontoTorontoCanada
  10. 10.Clinical Cooperation Unit Pediatric OncologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  11. 11.Department of Pediatric Oncology, Hematology and ImmunologyHeidelberg University HospitalHeidelbergGermany
  12. 12.National Center for Tumor Diseases (NCT)HeidelbergGermany
  13. 13.Department of NeurosurgeryUniversity Hospital TübingenTübingenGermany
  14. 14.Centre for Neurofibromatosis, Centre for Rare Diseases TübingenTübingenGermany
  15. 15.German Cancer Consortium (DKTK) Partner Site TübingenTübingenGermany
  16. 16.Department of NeurologyUniversity Hospital Hamburg-EppendorfHamburgGermany

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