TY - JOUR
T1 - Expression profiling of the ovarian surface kinome reveals candidate genes for early neoplastic changes
AU - Pejovic, Tanja
AU - Pande, Nupur T.
AU - Mori, Motomi
AU - Mhawech-Fauceglia, Paulette
AU - Harrington, Christina
AU - Mongoue-Tchokote, Solange
AU - Dim, Daniel
AU - Andrews, Christopher
AU - Beck, Amy
AU - Tarumi, Yukie
AU - Djilas, Jovana
AU - Cappuccini, Fabio
AU - Caballero, Otavia
AU - Huang, Jiaqi
AU - Levy, Samuel
AU - Tsiamouri, Alexia
AU - Cain, Joanna
AU - Bagby, Grover C.
AU - Strausberg, Robert L.
AU - Simpson, Andrew J.
AU - Odunsi, Kunle O.
PY - 2009
Y1 - 2009
N2 - 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 TGFβR1 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.DNAsequencing revealed two novelmutations 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.
AB - 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 TGFβR1 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.DNAsequencing revealed two novelmutations 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.
UR - https://www.scopus.com/pages/publications/77953375710
U2 - 10.1593/tlo.09199
DO - 10.1593/tlo.09199
M3 - Article
AN - SCOPUS:77953375710
SN - 1944-7124
VL - 2
SP - 341
EP - 349
JO - Translational Oncology
JF - Translational Oncology
IS - 4
ER -