Familial Cancer

, Volume 10, Issue 2, pp 337–342

Heterogeneity of familial medulloblastoma and contribution of germline PTCH1 and SUFU mutations to sporadic medulloblastoma

  • Ingrid Slade
  • Anne Murray
  • Sandra Hanks
  • Ajith Kumar
  • Lisa Walker
  • Darren Hargrave
  • Jenny Douglas
  • Charles Stiller
  • Louise Izatt
  • Nazneen Rahman
Article

DOI: 10.1007/s10689-010-9411-0

Cite this article as:
Slade, I., Murray, A., Hanks, S. et al. Familial Cancer (2011) 10: 337. doi:10.1007/s10689-010-9411-0

Abstract

PTCH1 and SUFU are both regulators of the sonic hedgehog signalling pathway. Germline inactivating mutations in both genes are associated with multisystem phenotypes including medulloblastoma. Somatic inactivating mutations in PTCH1 and SUFU each occur in approximately 10% of medulloblastomas. Recently, SUFU mutations were reported in familial medulloblastoma pedigrees without additional phenotypic features. We sought to further investigate the contribution of germline PTCH1 and SUFU mutations to familial and sporadic medulloblastoma. We performed full-gene mutational analysis of both PTCH1 and SUFU in three familial medulloblastoma pedigrees and 83 individuals with sporadic non-familial medulloblastoma. We identified no mutations in PTCH1 or SUFU in the three familial medulloblastoma pedigrees. We identified no PTCH1 mutations and two SUFU mutations that cause premature protein truncating in the series of sporadic non-familial medulloblastomas. The SUFU mutations were identified in two of the 16 individuals with desmoplastic medulloblastomas. These data indicate that familial medulloblastoma is a genetically heterogeneous disorder with at least one further susceptibility gene to be discovered. Furthermore, although both PTCH1 and SUFU play a key role in the sonic hedgehog signalling pathway, PTCH1 does not make an appreciable contribution to non-familial sporadic medulloblastoma, whereas inactivating germline mutations of SUFU cause ~2–3% of sporadic medulloblastomas and > 10% of desmoplastic medulloblastomas.

Keywords

Familial medulloblastoma Medulloblastoma PTCH1 SUFU Tumor predisposition 

Abbreviations

MBEN

Medulloblastoma with extensive nodularity

NBCCS

Nevoid basal cell carcinoma syndrome

CCLG

Children’s cancer and leukaemia group

PCR

Polymerase chain reaction

Supplementary material

10689_2010_9411_MOESM1_ESM.doc (62 kb)
Supplementary material 1 (DOC 61 kb)

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Ingrid Slade
    • 1
  • Anne Murray
    • 1
  • Sandra Hanks
    • 1
  • Ajith Kumar
    • 2
  • Lisa Walker
    • 3
  • Darren Hargrave
    • 4
  • Jenny Douglas
    • 1
  • Charles Stiller
    • 5
  • Louise Izatt
    • 6
  • Nazneen Rahman
    • 1
  1. 1.Section of Cancer GeneticsInstitute of Cancer Research and Royal Marsden HospitalSutton, SurreyUK
  2. 2.Department of Clinical GeneticsGreat Ormond Street HospitalLondonUK
  3. 3.Department of Clinical GeneticsChurchill HospitalHeadington, OxfordUK
  4. 4.Section of PaediatricsInstitute of Cancer Research and Royal Marsden HospitalSutton, SurreyUK
  5. 5.Childhood Cancer Research Group, Department of PaediatricsUniversity of OxfordOxfordUK
  6. 6.Department of Clinical GeneticsGuy’s and St Thomas’ HospitalLondonUK

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