Aberrant expression of TopBP1 in breast cancer.
OBJECTIVE
The TopBP1 protein includes eight BRCT domains (originally identified in BRCA1) and has homology with BRCA1 over the carboxyl terminal half of the protein. The aim of this study was to determine whether TopBP1 is aberrantly expressed in breast cancer.


RESULTS
Sixty-one breast carcinomas from an unselected consecutive patient cohort were studied along with 12 samples of breast tissue from cosmetic breast reduction surgery; these were analysed immunohistochemically for TopBP1 expression using a rabbit polyclonal antibody. This antibody was validated in immunoprecipitation and immunofluorescence experiments. Immunohistochemical analysis demonstrated that TopBP1 was expressed almost exclusively in the nuclei of the normal breast epithelium. However, in a significant number of breast carcinomas TopBP1 was aberrantly expressed, as it was detected in the cytoplasm and nucleus of some tumours and exclusively in the cytoplasm of others. In two out of 61 carcinomas investigated, no TopBP1 expression was detected.


CONCLUSIONS
For the first time this report demonstrates aberrant expression of the TopBP1 protein in breast carcinoma. We propose TOPBP1 as a breast cancer susceptibility gene.
Going
J J
JJ
Faculty of Medicine, Division of Cancer Sciences and Molecular Pathology, Division of Pathological Sciences, Faculty of Veterinary Medicine, University of Glasgow, Glasgow, UK. going@udcf.gla.ac.uk
Nixon
C
C
Dornan
E S
ES
Boner
W
W
Donaldson
M M
MM
Morgan
I M
IM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D042361:Mammary Glands, Human / Q000378:metabolism; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011817:Rabbits; D012016:Reference Values
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C110513:TOPBP1 protein, human