Allelic loss of cyclophilin 40, an estrogen receptor-associated immunophilin, in breast carcinomas.
OBJECTIVE
Cyclophilin 40 (CyP40) is an estrogen receptor-associated protein which appears to modify receptor function. The aim of this study was to determine the extent of allelic loss at the CyP40 locus in a panel of breast carcinomas using a newly characterized microsatellite marker located upstream of the CyP40 gene and then to correlate this with losses at chromosomal sites for cancer-associated genes.


METHODS
Allelic loss at CyP40 was determined from patients' matched tumor and normal breast tissue using Genescan 672 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 allelic loss were grade II or III invasive ductal carcinomas and generally showed multiple losses at other sites near known cancer-associated genes.


CONCLUSIONS
The polymorphic marker which we characterized was useful in determining allelic loss at the CyP40 locus in breast cancer patients and when applied 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.
Ward
B K
BK
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Center, Nedlands, Western Australia.
Kumar
P
P
Turbett
G R
GR
Edmondston
J E
JE
Papadimitriou
J M
JM
Laing
N G
NG
Ingram
D M
DM
Minchin
R F
RF
Ratajczak
T
T
D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D019696:Peptidylprolyl Isomerase / Q000235:genetics*; D011960:Receptors, Estrogen / Q000378:metabolism*
D002352:Carrier Proteins; D000081406:Peptidyl-Prolyl Isomerase F; D011960:Receptors, Estrogen; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase