High rates of loss of heterozygosity on chromosome 19p13 in human breast cancer

We have recently discovered that the nuclear matrix protein SAFB is an oest rogen receptor corepressor. Since it has become clear that many steroid rec eptor cofactors play important roles in breast tumorigenesis, we investigat ed whether SAFB could also be involved in breast cancer, To address this qu estion, the gene locus was examined for structural alterations in breast ca ncer tissue, Laser capture microdissection was used for isolating DNA from paired primary breast tumour and normal tissue specimens. and the loss of h eterozygosity (LOH) at chromosome 19p13.2-3 was determined by use of micros atellite markers. LOH was detected at the marker D19S216, which colocalizes with the SAFB locus, in specimens from 29 (78.4%) of 37 informative patien ts. The peak LOH rate occurred at D19S216 near the SAFB locus. with LOH fre quencies ranging from 21.6% to 47.2% at other markers. The finding of a ver y high LOH rate at the marker D19S216 strongly indicates the presence of a breast tumour-suppressor gene locus. While preliminary findings of mutation s in SAFB suggest that this indeed may be a promising candidate, other pote ntial candidate genes are located at this locus. (C) 2001 Cancer Research C ampaign.