Abstract:
:Three patients had supratentorial malignant brain tumors 7 to 9 years after prophylactic central nervous system (CNS) treatment for acute lymphocytic leukemia or malignant T-cell lymphoma. Therapy was administered at the age of 3 to 8 years and included cranial irradiation (total dose, 1800 to 2400 cGy) and intrathecal methotrexate. The brain tumors had histologic and immunohistochemical features of primitive neuroectodermal tumors (PNET), including neuroblastic rosettes, rhythmic arrangement of tumor cells, and immunohistochemical expression of glial, and in one patient neuronal, marker proteins. Using polymerase chain reaction-mediated DNA amplification from paraffin-embedded tissues and subsequent DNA sequence analysis, an activating point mutation was detected in the K-ras protooncogene in one tumor. This mutation was a G to A transition in position 2 of codon 12, substituting aspartate (GAT) for glycine (GGT). This type of mutation has not been observed before in human brain tumors, but it is frequent in radiation-induced murine lymphomas. These observations suggest that PNET can be induced after completion of the embryonal and fetal development of the human CNS. Oncogene-activating point mutations may represent a pathogenetic mechanism involved in the genesis of radiation-induced brain tumors.
journal_name
Cancerjournal_title
Cancerauthors
Brüstle O,Ohgaki H,Schmitt HP,Walter GF,Ostertag H,Kleihues Pdoi
10.1002/1097-0142(19920501)69:9<2385::aid-cncr2820subject
Has Abstractpub_date
1992-05-01 00:00:00pages
2385-92issue
9eissn
0008-543Xissn
1097-0142journal_volume
69pub_type
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