Deletion of chromosome arm 17p dna sequences in pediatric high-grade and juvenile pilocytic astrocytomas

✍ Scribed by Jennifer R. Willert; Laleh Daneshvar; Val C. Sheffield; Philip H. Cogen

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 692 KB
• Volume: 12
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.2870120303

✦ Synopsis

In adults, loss of het.erozygosity for DNA on I7p has been shown in high-grade anaplastic astrocytomas (AAs) and glioblastomas multiforme (GMs), and mutation of the TP53 tumor suppressor gene has been reported in all grades of astrocytomas. Little is known, however, about I7p deletion and TP53 mutation in juvenile pilocytic astrocytomas (JPAs), the most common low-grade tumors seen in children. To elucidate the genetic characteristics of pediatric high-grade astrocytomas and JPAs, we performed restriction fragment length polymorphism analysis with probes derived from I7p and TP53 mutational studies in 28 tumor specimens. Telomeric chromosome arm I7p markers 144-D6 and ABR were lost in 6 (75%) of 8 informative tumors classified as high-grade (7 A h , I GM) and in 2 (I 0%) of 20 informative JPAs. Loss of I7p probes centromeric t o the TP53 gene were also detected in 3 A A s and 5 JPAs. Four of the 6 (66%) JPAs with losses of 17p DNA sequences recurred rapidly despite aggressive therapy, whereas only 5 of the other 14 (36%) recurred. Mutation of the TP53 gene was detected by polymerase chain reaction and denaturing gradient gel electrophoresis in only I JPA and I AA. These tumors were also examined for MDMZ gene amplification as an alternate inactivation mechanism for TP53 gene function: no instances of alteration were 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-grade astrocytomas and aggressive JPAs in children. Further, molecular genetic studies may be an important supplement t o current clinical and radiologic data in predicting the outcome and guiding the therapy of children with aggressive and malignant astrocytomas. Genes Chrornosorn Cancer 12:165-/72 (1995).