Background: The most common cytogenetic abnormality encountered in primitive neuroectodermal tumors (PNET)/medulloblastoma is loss of heterozygosity in the region of the short arm of chromosome 17. There is some evidence that supratentorial PNET has different cytogenetic markers than infratentorial PNET/medullo-blastoma. Particularly, loss of 17p is more frequent in the latter than in the former. We describe a young girl diagnosed with supratentorial PNET (SPNET). Analysis of the tumor suppressor gene p53 in the tumorous tissue revealed a rare transversion mutational event of CAT to AAT in position 179 of exon 5. To the best of our knowledge, this is the first case of such a transversion at codon 179 in the p53 gene in SPNET. Case Report: A 12-year-old girl was admitted with nausea, headache and vision disturbances. MRI of the brain showed a large space-occupying lesion in the right frontal lobe. Histological examination of the macroscopic resection of the tumor revealed PNET of the brain. Polymerase chain reaction-single strand conformation polymorphism analysis of all p53 exons was performed, and a unique variant of a transversion at codon 179 of exon 5 was revealed. Therapy was started according to the Children's Cancer group protocol (CCG-99702) designated for treatment of high-risk central nervous system embryonal tumors. She received an initial course of chemotherapy, consisting of cyclophosphamide and vincristine for mobilizing and harvesting peripheral blood stem cells (PBSCs). Then she was given craniospinal irradiation (3,600 cGy) with a boost to the tumor bed (1,980 cGy) and three consecutive courses of high-dose chemotherapy with carboplatin, vincristine and thiotepa/cyclophosphamide, with PBSCs support after each course. Results: The patient is in complete remission 17 months after diagnosis, based on the results of physical examination and imaging studies. Discussion: The mutation results in an alteration of the amino acid HIS to ASN. The amino acids surrounding position 175 play an important role in stabilizing the p53/DNA complex. There are only 12 known mutations of the reported type, and the finding of such a rare mutational event in a low-incidence p53 mutation tumor, such as SPNET, might add additional insight into the p53-SPNET relationship in tumorigenesis. Although not widely accepted, it is possible that different mutations of the p53 gene in patients with brain tumors may imply a different ultimate prognosis. In our case, we cannot exclude the fact that transversion of CAT to AAT in position 179 of exon 5 may explain prolonged survival of a patient with good response to therapy.
- Gene mutation
- Mutational event
- Supratentorial primitive neuroectodermal tumor