TUMORIGENICITY OF CEREBELLAR PRIMITIVE NEURO-ECTODERMAL TUMORS IN ATHYMIC MICE CORRELATES WITH POOR-PROGNOSIS IN CHILDREN

The histogenesis of medulloblastoma, also described as a cerebellar pr imitive neuro-ectodermal tumor (PNET), remains controversial and unres olved. In addition, genetic markers which characterize cerebellar PNET s with poor prognosis in not been identified, Since xenografts can be for better understanding the genetic events involved in cerebellar PNE Ts, small fragments of tumor samples from 17 children with newly diagn osed cerebellar PNETs were transplanted s.c. into female athymic Swiss mice. Eleven were non-metastatic and 6 were metastatic PNETs. Eight t umors (47%) were tumorigenic. Histological analysis showed 6 typical m edulloblastomas, 1 PNET with melanin pigment and 1 PNET with a rhabdoi d phenotype, Wide heterogeneity was observed in tumor growth, with a d oubling time ranging from 8 to 81 days after the first passage, Tumori genicity was correlated with the metastatic phenotype of the tumor (p < 0.001). All the patients but one with a tumorigenic tumor relapsed a nd died. The survival of patients with a non-tumorigenic PNET (67%) wa s significantly higher than that of patients with a tumorigenic PNET ( 13%) (P < 0.02). None of the xenografts or tumors from patients exhibi ted N-myc-gene alteration. Only one xenograft showed c-myc amplificati on, with an abnormal 15-kilobase fragment. None of the 17 tumors from patients showed amplification or c-myc-gene rearrangement. In conclusi on, tumorigenicity of cerebellar PNETs strongly correlates both with t he metastatic phenotype of the tumors and with the disease-free surviv al of the patients. In addition, genetic events other than c-myc-gene amplification might be involved in cerebellar PNETs with poor prognosi s. (C) 1996 Wiley-Liss, Inc.