A DELETION POLYMORPHISM DUE TO ALU-ALU RECOMBINATION IN INTRON-2 OF THE RETINOBLASTOMA GENE - ASSOCIATION WITH HUMAN GLIOMAS

The retinoblastoma gene (RE) encodes a tumor suppressor that is inacti vated in a number of different types of cancer. We searched for gross alterations of this gene in tumors of the central nervous system by us ing Southern blot hybridization. A common alteration was found in seve ral tumors and was mapped to the region around exon 2. Nucleotide sequ encing showed that the alteration was caused by a 799-bp deletion in i ntron 2 of the RE gene and was probably due to homologous recombinatio n between two Alu repeats. Deletions of this type have not been found previously in the RE gene. The deletion turned out to be a polymorphis m with an allele frequency estimated at 2.2% in 185 patients without c ancer. The deletion was found in five of 48 patients with brain tumors (allele frequency of 5.2%). This difference is not statistically sign ificant (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 e xact test). Further study is needed to determine if the deletion is a weak brain cancer-predisposing mutation or a harmless polymorphism. Fi nding this mutation in a tumor and the germline DNA of a retinoblastom a patient could lead to incorrect estimation of the heritability of a tumor. (C) 1997 Wiley-Liss, Inc.