Klin Padiatr 2017; 229(03): 182-195
DOI: 10.1055/s-0037-1602207
Top 3 Solid tumors
Georg Thieme Verlag KG Stuttgart · New York

Evidence for TCF4 playing a role as tumor suppressor in medulloblastoma

M Lauffer
1   Center for Neuropathology, LMU Munich
,
M Hellwig
2   Research Institute Children's Cancer Center Hamburg
3   Department for Pediatric Hematology and Oncology, UKE Hamburg
,
U Schüller
1   Center for Neuropathology, LMU Munich
2   Research Institute Children's Cancer Center Hamburg
3   Department for Pediatric Hematology and Oncology, UKE Hamburg
4   Institute for Neuropathology, UKE Hamburg, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
30 May 2017 (online)

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    Introduction:

    The bHLH transcription factor 4 (TCF4) is involved in the development of the central nervous system by initiating neural differentiation. Recently, TCF4 has been shown to be mutated in about 15% of adult SHH-associated medulloblastoma. However, the functional role of TCF4 in the development of medulloblastoma is unclear.

    Methods:

    We investigated the expression of TCF4 in human medulloblastoma samples and correlated expression pattern and mutational status with patients' clinical outcome. We further introduced mutated TCF4 in living tumor cells and deleted Tcf4 from murine cerebellar granule precursors.

    Results:

    Expression of TCF4 in SHH medulloblastoma correlated with a better clinical outcome. Expression of WT TCF4 in medulloblastoma cells decreased cell proliferation, whereas TCF4 mutants proved to have lost their suppressive function. Furthermore, a loss of Tcf4 in cerebellar granule neuron precursors increased proliferation.

    Conclusions:

    Our results suggest a tumor-suppressive role for TCF4 in SHH medulloblastoma.


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    No conflict of interest has been declared by the author(s).