The BRK tyrosine kinase is expressed in high-grade serous carcinoma of the ovary.
BACKGROUND
We identified the BRK tyrosine kinase in a PCR-based screen of tyrosine kinases expressed by ovarian tumors. BRK expression is restricted to normal differentiating epithelial cells and its overexpression may play a role in processes related to tumor development and growth. Its expression in normal ovary and ovarian tumors has not previously been described, and is the focus of this study.


METHODS
BRK expression levels were determined in 14 normal ovaries and 138 high-grade, late stage serous carcinomas of the ovary by immunohistochemical analysis, and in 19 ovarian cancer cell lines and immortalized ovarian surface epithelium by Western blot analysis. Furthermore, BRK/PTK6 gene copy number was determined in seven primary serous carcinomas by fluorescence in situ hybridization.


RESULTS
Immunohistochemical studies indicate that BRK is highly expressed in 97/138 (70%) of high-grade, serous carcinomas of the ovary, but is absent in normal ovarian surface epithelia. BRK is also expressed by 9/19 of ovarian cancer cell lines, but is undetectable in immortalized ovarian surface epithelium. Interestingly, the BRK gene has been mapped to chromosome 20q13.3, a site frequently amplified in ovarian cancers, and associated with poor prognosis. We have determined by fluorescence in situ hybridization (FISH) that BRK is specifically amplified at low levels in 6/7 primary ovarian carcinomas.


CONCLUSIONS
The amplification of the BRK gene and overexpression of BRK protein in the majority of high-grade serous carcinomas and ovarian cancer cell lines suggest that BRK may play a role in the development and growth of ovarian tumors.
Schmandt
Rosemarie E
RE
Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77230-1439, USA. rschmand@mdanderson.org
Bennett
Marsha
M
Clifford
Stephanie
S
Thornton
Angela
A
Jiang
Feng
F
Broaddus
Russell R
RR
Sun
Charlotte C
CC
Lu
Karen H
KH
Sood
Anil K
AK
Gershenson
David M
DM
D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018284:Cystadenocarcinoma, Serous / Q000201:enzymology* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D009363:Neoplasm Proteins; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human