Comparison of constitutional and tumor-associated 11;22 translocations: nonidentical breakpoints on chromosomes 11 and 22.

Recurring, site-specific chromosomal rearrangements are associated with several human syndromes and malignant disorders. Such nonrandom translocations involving chromosome 22 in band q11 are numerous and found to be associated with a diversity of neoplasms as well as constitutional disorders. Chromosome 11 in bands q23-q24 is similarly involved in several types of tumors as well as in a recurring constitutional reciprocal translocation with chromosome 22. Here we report the use of chromosomal in situ hybridization to compare the translocation breakpoints in the cytologically indistinguishable constitutional t(11;22) and the tumor-related t(11;22) associated with Ewing sarcoma and peripheral neuroepithelioma. We have shown that the breakpoints can be distinguished from each other with respect to the locus encoding the constant region of the Ig lambda light chain (C lambda) at 22q11 and the ETS1 locus at 11q23----q24; ETS1 has been called hu-ets-1 or human c-ets-1. The tumor-associated chromosome 11 breakpoint is also different from those of leukemias with t(9;11) and t(4;11) translocations. Southern-blot analysis showed no rearrangement of ETS1 in these disorders in the region detected by our probe. ETS1 has also been mapped more precisely to 11q23.3----q24 by in situ hybridization to cells from an individual with an 11q23.3----qter deletion.