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


METHODS
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.
Pejovic
Tanja
T
Division of Gynecologic Oncology, Oregon Health & Science University, Portland, OR 97239, USA.
Pande
Nupur T
NT
Mori
Motomi
M
Mhawech-Fauceglia
Paulette
P
Harrington
Christina
C
Mongoue-Tchokote
Solange
S
Dim
Daniel
D
Andrews
Christopher
C
Beck
Amy
A
Tarumi
Yukie
Y
Djilas
Jovana
J
Cappuccini
Fabio
F
Caballero
Otavia
O
Huang
Jiaqi
J
Levy
Samuel
S
Tsiamouri
Alexia
A
Cain
Joanna
J
Bagby
Grover C
GC
Strausberg
Robert L
RL
Simpson
Andrew J
AJ
Odunsi
Kunle O
KO