MOLECULAR-GENETIC EVIDENCE FOR SUBTYPES OF OLIGOASTROCYTOMAS

The histogenesis of oligoastrocytomas remains controversial, with some data arguing similarity of oligoastrocytomas to astrocytic tumors, an d other data suggesting closer relationships with oligodendroglial neo plasms. Since the molecular genetic changes in astrocytomas differ fro m those of oligodendrogliomas, we characterized 120 astrocytic and oli godendroglial tumors, including 38 oligoastrocytomas, for genetic alte rations that occur disproportionately between astrocytomas and oligode ndrogliomas, i.e. TP53 gene mutations and allelic loss of chromosomes Ip, 17p and 19q. As previously reported, TP53 mutations were common in astrocytic gliomas, occurring in approximately half of WHO grade II a nd III astrocytomas, but in only 5% of WHO grades II and III oligodend rogliomas. Allelic losses of chromosomes Ip and 19q, however, were com mon in oligodendrogliomas (41% and 63%), but less frequent in astrocyt omas (9% and 35%). Oligoastrocytomas showed TP53 mutations in 12/38 (3 2%) cases and allelic losses of chromosomes Ip and 19q in 52% and 70%, respectively. Most importantly, TP53 mutations and allelic losses on chromosomes Ip and 19q were inversely correlated in oligoastrocytomas (p < 0.011 and p < 0.019). These data suggest the existence of two gen etic subsets of oligoastrocytomas, one genetically related to astrocyt omas and the other genetically related to oligodendrogliomas. Histolog ically, those oligoastrocytomas with TP53 mutations were more often as trocytoma-predominant, while those with chromosome 19q loss were more often oligodendroglioma-predominant.