Allelic loss of cyclophilin 40, an estrogen receptor-associated immunophilin, in breast carcinomas

Purpose: Cyclophilin 40 (CyP40) is an estrogen receptor-associated protein which appears to modify receptor function. The aim of this study was to det ermine the extent of allelic loss at the CyP40 locus in a panel of breast c arcinomas using a newly characterized microsatellite marker located upstrea m of the CyP40 gene and then to correlate this with losses at chromosomal s ites for cancer-associated genes. Methods: Allelic loss at CyP40 was determ ined from patients' matched tumor and normal breast tissue using Genescan 6 72 software analysis of fluorescently labeled, PAGE-separated PCR products incorporating the marker. For each patient, allelic loss at CyP40 was then assessed and compared with losses at markers for various cancer-associated genes. Results: Allelic loss was detected in 30% of breast carcinomas from patients heterozygous for the CyP40 marker. All carcinomas demonstrating al lelic loss were grade II or III invasive ductal carcinomas and generally sh owed multiple losses at other sites near known cancer-associated genes. Con clusions: The polymorphic marker which we characterized was useful in deter mining allelic loss at the CyP40 locus in breast cancer patients and when a pplied in these studies in conjunction with various cancer-associated gene markers, suggests that deletions in the region of the CyP40 gene might be a late event in breast tumor progression.