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Published on: July 25, 2020
The BRK tyrosine kinase is expressed in high-grade serous carcinoma of the ovary
Rosemarie E Schmandt1, Marsha Bennett, Stephanie Clifford
1Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77230-1439, USA. rschmand@mdanderson.org
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.
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