D11S146 and BCL1 are physically linked but can be discriminated by their amplification status in human breast cancer

Band q13 of chromosome 11 is frequently altered in a number of human cancers. We have undertaken physical mapping in this region, starting with D11S146, an anonymous 11q13 DNA fragment. This probe has been used by others as a landmark to locate MEN1, a locus of predisposition to multiple endocrine neoplasia. Long-range restriction mapping locates D11S146 within approximately 400 kb of the BCL1 translocation breakpoint involved in certain B-cell malignancies. BCL1 and two proto-oncogenes, INT2 and HST, were previously found to be coamplified in approximately 1/5 breast carcinomas. Although close to BCL1, D11S146 is present in less than 3/4 of these amplification units and delimits their centromeric boundary. Therefore, we propose that D11S146 defines two genetic regions. The centromeric region--PYGM/D11S146--contains MEN1. The telomeric one includes the D11S146/BCL1/INT2/HST area and is relevant to DNA amplification in carcinomas and to B-cell translocations.