DELETION OF CHROMOSOME ARM 17P DNA-SEQUENCES IN PEDIATRIC HIGH-GRADE AND JUVENILE PILOCYTIC ASTROCYTOMAS

In adults, loss of heterozygosity for DNA on 17p has been shown in hig h-grade anaplastic astrocytomas (AAs) and glioblastomas multiforme (GM s), and mutation of the TP53 tumor suppressor gene has been reported i n all grades of astrocytomas. Little is known, however, about 17p dele tion and TP53 mutation in juvenile pilocytic astrocytomas (JPAs), the most common low-grade tumors seen in children. To elucidate the geneti c characteristics of pediatric high-grade astrocytomas and JPAs, we pe rformed restriction fragment length polymorphism analysis with probes derived from 17p and TP53 mutational studies in 28 tumor specimens. Te lomeric chromosome arm 17p markers 144-D6 and ABR were lost in 6 (75%) of 8 informative tumors classified as high-grade (7 AAs, I GM) and in 2 (10%) of 20 informative JPAs. Loss of 17p probes centromeric to the TP53 gene were also detected in 3 AAs and 5 JPAs. Four of the 6 (66%) JPAs with losses of 17p DNA sequences recurred rapidly despite aggres sive therapy, whereas only 5 of the other 14 (36%) recurred. Mutation of the TP53 gene was detected by polymerase chain reaction and denatur ing gradient gel electrophoresis in only I JPA and I AA. These tumors were also examined for MDM2 gene amplification as an alternate inactiv ation mechanism for TP53 gene function: no instances of alteration wer e identified. These results suggest that a gene or genes in addition t o TP53 on 17p may be involved in the etiology or progression of high-g rade astrocytomas and aggressive JPAs in children. Further, molecular generic studies may be an important supplement to current clinical and radiologic data in predicting the outcome and guiding the therapy of children with aggressive and malignant astrocytomas. (C) 1995 Wiley-Li ss, Inc.