Fig. 6.

APE1 is a tumor suppressor. (A) All mice with dual APE1 and p53 inactivation [(Ape1;p53)^Nes-cre] and many that were p53-heterozygous [i.e., (Ape1^L/L;p53^L/+)^Nes-cre] developed brain tumors at 1–3 mo of age. Control mice were Ape1 WT, p53^Nes-cre. (B) Histology of a representative (Ape1;p53)^Nes-cre and (Ape1^L/L;p53^+/L)^Nes-cre medulloblastoma is shown. (Upper) H&E and Nissl staining indicates typical tumor presence in the molecular layer of the cerebellum. (Lower) Immunostaining for PCNA indicates tumor cell proliferation. (C) Immunostaining for MATH1 indicates that the medulloblastoma is a sonic hedgehog-driven tumor derived from granule neuron precursors. P5 developing cerebellum shows normal MATH1 levels in immature granule neurons in the molecular layer. Corresponding medulloblastoma sections indicate widespread MATH1 immunopositivity in tumor tissue. GC, granule cells; MB, medulloblastoma. (D) Recurrent cytogenetic abnormalities are present in the tumors, including loss of Ptch1 and loss of a copy of Chr13 (which contains Ptch1) and MycN amplification. Mixt, the N-myc amplification was heterogeneous and not identified in all tumor cells. (E) Cytogenetic analysis utilizing FISH indicates the loss of Patched-1 and in some cases chromosome 13 (arrow). (F) Amplification of MycN is also observed in many medulloblastomas and often appears as an homogeneously stained region in the chromatin (arrows). The FISH images represent two of the five tumors listed in the table in D.