Structure and expression of the c-sis gene and its relationship to sporadic meningiomas

A deletion in an Alu repetitive sequence in the fifth intron of the c-sis gene of meningioma patients was previously described (M. Smidt et al., J. Clin. Invest., 86:1151-1157, 1990). The authors analyzed the structure of this intron in DNA from peripheral blood leukocytes and tumor samples of 86 patients with sporadic meningiomas. After amplifying these DNA sequences by the polymerase chain amplification reaction, the authors failed to find any cases with deletions. They also analyzed the effects on the expression of c-sis of the fifth intron with or without the deletion. A c-sis expression clone with an SV40 promoter was modified by adding introns 4, 5, and 6, and the resulting clones were used to examine the expression of c-sis mRNA in A172, NIH3T3, and Cos-7 cells. Northern blots showed that the quantity of message was not changed when the introns were present and that the size of the message was not changed by the deletion in the fifth intron. The effect of the fifth intron Alu sequence on the c-sis promoter was also tested using clones with chloramphenicol acetyltransferase as a reporter gene in A172 and Cos-7 cells. The c-sis promoter was not affected by the fifth intron Alu sequence with or without the deletion and in either orientation. There were also no effects when cells were stimulated by phorbol 12-myristate 13-acetate or the regulatory gene Tax from human T-lymphotropic virus type 1. These data do not support a role for deletions in the fifth c-sis intron in the development of most sporadic meningiomas.