Alternative splicing of neurofibromatosis type 1 gene transcript in malignant brain tumors: PCR analysis of frozen‐section mRNA

The neurofibromatosis type 1 (NF1) gene encodes a 360‐residue region showing significant homology to the catalytic domains of both mammalian GTPase‐activating protein (GAP) and yeast IRA protein. The product of the GAP‐related domain of the NF1 gene (NF1‐GRD) has been shown to stimulate ras GTPase and consequently to inactivate ras protein. We previously reported that the NF1‐GRD has two types of transcripts, type I and type II, which are generated by an alternative splicing mechanism, and that the differential splicing of the NF1‐GRD may be related to differentiation of neuroectodermal cells. Here we examined the differential expression of type I and type II transcripts of NF1‐GRD in clinical samples of supratentorial malignant brain tumors by the RNA‐polymerase chain reaction (PCR) method using frozen tissue sections. Our observations revealed that normal cerebrum predominantly expressed the type II NF1‐GRD transcript, whereas primitive neuroectodermal tumors predominantly expressed the type I transcript. Additionally, although the type I/type II ratio in astrocytomas varied widely among tissue samples, all glioblastomas showed higher type I/type II ratios than adjacent brain samples. The RNA‐PCR analysis using frozen tissue sections is a useful and sensitive method for detecting genetic markers in clinical tissue samples. © 1992 Wiley‐Liss, Inc.