Evidence for TCF4 playing a role as tumor suppressor in medulloblastoma

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.