A gene called "prohibitin" was isolated as a candidate antiproliferating gene in rat liver cells. We have isolated the human homologue of the rat prohibitin gene and mapped it to chromosome 17q12-21 where a gene responsible for hereditary breast cancer was localized. DNA sequence analysis of 2 exons in this gene in 23 sporadic breast cancers, which showed loss of heterozygosity on the long arm of chromosome 17 or developed in patients 35 years old or younger, identified 4 cases of somatic mutation; 2 of these were missense mutations; 1 showed a 2-base deletion resulting in truncation of the gene product due to a frame shift; the other had a C to T transition in an intron adjacent to an intron-exon boundary. These results suggest that this gene may be a tumor suppressor gene and is associated with tumor development and/or progression of at least some breast cancers.