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American Journal of Pathology, Vol 149, 621-627, Copyright © 1996 by American Society for Investigative Pathology

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Up-regulation of specific NF 1 gene transcripts in sporadic pilocytic astrocytomas

M Platten, MJ Giordano, CM Dirven, DH Gutmann and DN Louis
Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, Boston 02114, USA.

Pilocytic astrocytomas of the optic nerve (optic nerve gliomas) are closely associated with neurofibromatosis 1 (NF1), and allelic losses of the NF1 gene region on chromosome 17q occur in sporadic pilocytic astrocytomas. We therefore hypothesized that the NF1 gene acts as a tumor suppressor gene in pilocytic astrocytomas, and that NF1 gene expression would be reduced or absent in these tumors. To evaluate this possibility, we examined quantitative and qualitative aspects of NF1 gene expression in six sporadic pilocytic astrocytomas. Surprisingly, the NF1 gene was overexpressed up to fourfold in these tumors when compared with normal brain. This up-regulation was accompanied by immunohistochemical positivity using a carboxyl-terminal antibody and by the absence of mutations in one kilobase of the NF1 coding sequence, consistent with the expressed transcript and protein being full length and probably wild type. Pilocytic astrocytomas showed a marked predominance of transcripts containing exon 23a and lacking exon 9br, the same isoforms that are expressed by normal and reactive astrocytes and malignant astrocytomas. These data illustrate that pilocytic astrocytomas overexpress specific NF1 gene transcripts, perhaps as a regulatory response to growth stimuli. The role of the NF1 gene as a tumor suppressor in pilocytic astrocytomas, however, remains to be proven.

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