Expression profiling of the ovarian surface kinome reveals candidate genes for early neoplastic changes.

OBJECTIVES We tested the hypothesis that co-coordinated up-regulation or down-regulation of several ovarian cell surface kinases may provide clues for better understanding of the disease and help in rational design of therapeutic targets. STUDY DESIGN We compared the expression signature of 69 surface kinases in normal ovarian surface epithelial cells (OSE), with OSE from patients at high risk and with ovarian cancer. RESULTS Seven surface kinases, ALK, EPHA5, EPHB1, ERBB4, INSRR, PTK, and TGFbetaR1 displayed a distinctive linear trend in expression from normal, highrisk, and malignant epithelium. We confirmed these results using semiquantitative reverse transcription-polymerase chain reaction and tissue array of 202 ovarian cancer samples. A strong correlate was shown between disease-free survival and the expression of ERBB4. DNA sequencing revealed two novel mutations in ERBB4 in two cancer samples. CONCLUSIONS A distinct subset of the ovarian surface kinome is altered in the transition from high risk to invasive cancer and genetic mutation is not a dominant mechanism for these modifications. These results have significant implications for early detection and targeted therapeutic approaches for women at high risk of developing ovarian cancer.