The identification of SUFU mutations in desmoplastic medulloblastoma provides new insights into vertebrate Hedgehog signaling and brain tumor formation.
These data indicate that germline SUFU mutations were responsible for a high proportion of desmoplastic medulloblastoma in children younger than 3 years of age.
The authors present the case of a 2.5-year-old African-American boy with desmoplastic medulloblastoma (MB) and nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, an autosomal dominant disorder resulting from mutations in the patched (PTCH) gene that predisposes to neoplasias (including basal cell carcinomas [BCCs] and MB) and to widespread congenital malformations.
Further analysis of the 9p and 17q22-q24 amplicons by array-based CGH (matrix-CGH) and candidate gene analyses revealed amplification of JMJD2C at 9p24 in one DMB and amplification of RPS6KB1, APPBP2, PPM1D and BCAS3 from 17q23 in three DMBs.
Among the 17q23 genes, RPS6KB1 showed markedly elevated transcript levels as compared to normal cerebellum in five of six DMBs and four of five classic medulloblastomas investigated.
Further analysis of the 9p and 17q22-q24 amplicons by array-based CGH (matrix-CGH) and candidate gene analyses revealed amplification of JMJD2C at 9p24 in one DMB and amplification of RPS6KB1, APPBP2, PPM1D and BCAS3 from 17q23 in three DMBs.
These data suggest that deregulated expression of PAX5 correlates positively with cell proliferation and inversely with neuronal differentiation in desmoplastic medulloblastoma.
Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB) (OS p<0.001, EFS p<0.001), SHH subgroup (OS p = 0.020, EFS p = 0.049) and WNT subgroup (OS p = 0.003, EFS p = 0.016) but not in desmoplastic/nodular medulloblastoma (DMB) (OS p = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055).
Our study showed postoperative primary CHT significantly influence the survival of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of MB.