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

Abstract

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 ≈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 ≈ 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 D11 S146 —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.