KA, B S , F M ), Sweden Deletions of the short arm of chromosome 3 and associated allele losses have been reported in the majority of sporadic renal cell carcinomas (RCC). O n the basis of the combined cytogenetic and molecular data, it is reasonable to assume that a putative RCC locus, which contributes t o tumor development by its loss, is located telomerically of the D3F15S2 site. Using H3E4, a D3FISSZ-specific probe, we have isolated a cDNA clone (c1.4-2). and a sequence comparison revealed that the c D N A clone corresponds t o the human acyl-peptide hydrolase gene. The gene is fairly universally expressed, but in RCC biopsies its expression is severely reduced, compared t o the normal kidney. C1.4-2 was used for in situ hybridization on metaphase chromosomes prepared from an Epstein-Barr virus (EBV) transformed lymphoblastoid cell line, derived from a t(3;8) (p14.2;q24.1) carrying member of the RCC family described by Cohen et al. in 1979 (N Engl 1 Med: 301:592-595). Carriers of this translocation regularly develop RCC by middle age. W e now report that D3F I5S2 is localized on the telomeric side of the constitutional breakpoint, in 3p2 I. The region of 3p affected by this familial translocation is thus not identical with the region of 3p most frequently deleted in sporadic RCC.