An abnormality in the c-sis protooncogene was identified in leukocyte DNA from members of a family predisposed to the development of meningioma, and was found to be associated with the development of the tumor in those individuals. Molecular analysis of this abnormality demonstrated a deletion within the fifth intron of the c-sis gene. The normal c-sis gene has an Alu sequence in this region which includes two perfect 130 nucleotide repeated sequences separated by 5 bp. The deleted c-sis allele is missing precisely one copy of the 130 bp repeat and the intervening 5 bp. An identical deletion was also found in DNA from 1 of 13 sporadic meningiomas.