Mapping by chromosome sorting of several gene probes, including C-myc, to the derivative chromosomes of a 3;8 translocation associated with familial renal cancer

Abstract

In eight members of a single family a constitutional translocation t(3;8) (p14.2;q24.1) is associated with the development of renal cancer. Chromosomes isolated from a cell line established from a subject with this translocation were analysed in flow with a fluorescence‐activated cell sorter (FACS II). Nearly six million chromosomes from the flow karyotype region containing the der(8) and 5.5 million from the region containing the der(3) were sorted, the DNA extracted, digested with EcoRI, size fractionated by electrophoresis, and transferred to nitrocellulose. Hybridization with gene probes for c‐mos, which has been localized to 8qll‐q22 and so‐matostatin, which has been mapped to 3q28, confirmed that the sorted fractions contained, respectively, the der(8) and der(3) chromosomes. The cellular oncogenes c‐raf‐1 (3p25) and c‐myc (8q24) were found to be translocated to the der(8) and der(3) chromosomes, respectively. The possible role that the relocation of c‐myc might have on the development of renal carcinoma in carriers of this 3;8 translocation was further studied by analysis of the region surrounding the c‐myc gene. By the use of cosmid cloning, no rearrangement 31 Kb 5′(or 19 Kb 3′) of the translocated gene was found, indicating that the breakpoint is not immediately adjacent to c‐myc. In an associated study, the DNA fragment D3S2 from chromosome 3 was found to map to 3p14.2‐pter. This assignment in conjunction with published somatic cell hybrid data enabled D3S2 to be mapped more precisely to the interval 3p14.2–3p21.