A deletion polymorphism due to Alu-Alu recombination in intron 2 of the retinoblastoma gene: association with human gliomas.

Abstract

The retinoblastoma gene (RB) encodes a tumor suppressor that is inactivated in a number of different types of cancer. We searched for gross alterations of this gene in tumors of the central nervous system by using Southern blot hybridization. A common alteration was found in several tumors and was mapped to the region around exon 2. Nucleotide sequencing showed that the alteration was caused by a 799-bp deletion in intron 2 of the RB gene and was probably due to homologous recombination between two Alu repeats. Deletions of this type have not been found previously in the RB gene. The deletion turned out to be a polymorphism with an allele frequency estimated at 2.2% in 185 patients without cancer. The deletion was found in five of 48 patients with brain tumors (allele frequency of 5.2%). This difference is not statistically significant (P = 0.149, Fisher's exact test). Confining the analysis only to glioma brain tumors revealed a statistically significant difference compared with the cancer-free patient controls (P = 0.027, Fisher's exact test). Further study is needed to determine if the deletion is a weak brain cancer-predisposing mutation or a harmless polymorphism. Finding this mutation in a tumor and the germline DNA of a retinoblastoma patient could lead to incorrect estimation of the heritability of a tumor.