Mapping the chromosome 16 cadherin gene cluster to a minimal deleted region in ductal breast cancer

The cadherin family of cell adhesion molecules has been implicated in tumor metastasis and progression. Eight family members have been mapped to the l ong arm of chromosome 16. Using radiation hybrid mapping, we have located s ix of these genes within a cluster at 16q21-q22.1. In invasive lobular carc inoma of the breast frequent LOH and accompanying mutation affect the CDHI gene, which is a member of this chromosome 16 gene cluster. CDHI LOH also o ccurs in invasive ductal carcinoma, but in the absence of gene mutation. Th e proximity of other cadherin genes to 16q22.1 suggests that they may be af fected by LOH in invasive ductal carcinomas. Using the mapping data, micros atellite markers were selected which span regions of chromosome 16 containi ng the cadherin genes. In breast cancer tissues, a high rate of allelic los s was found over the gene cluster region, with CDHI being the most frequent ly lost marker. In invasive ductal carcinoma a minimal deleted region was i dentified within part of the chromosome 16 cadherin gene cluster. This prov ides strong evidence for the existence of a second 16q22 suppressor gene lo cus within the cadherin cluster. (C) 2001 Elsevier Science Inc. All rights reserved.