Intragenic reorganization of RB1 in a complex (4;13) rearrangement demonstrated by FISH.

Reciprocal chromosome translocations with no apparent loss of material are the most common de novo structural rearrangements in man. The large majority of these cases have been characterized cytogenetically but very few have been investigated at the molecular level. Using fluorescence in situ hybridization (FISH) we have studied the organization of the tumor suppressor gene RB1 in a patient with retinoblastoma and a rearrangement between chromosomes 4 and 13. In addition to the hybridization signal on the normal chromosome 13, three distinct sites of hybridization of RB1 probes on the translocated chromosomes were detected. These findings show that a complex rearrangement occurred involving at least three breaks on chromosome 13, two of them in the RB1 gene. This also demonstrates that FISH, which offers resolution between that of fine molecular methods and classical cytogenetics, is a valuable tool for investigating organization of sequences at breakpoints of chromosomal rearrangements.