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

Tanja Pejovic; Nupur T. Pande; Motomi Mori; Paulette Mhawech-Fauceglia; Christina Harrington; Solange Mongoue-Tchokote; Daniel Dim; Christopher Andrews; Amy Beck; Yukie Tarumi; Jovana Djilas; Fabio Cappuccini; Otavia Caballero; Jiaqi Huang; Samuel Levy; Alexia Tsiamouri; Joanna Cain; Grover C. Bagby; Robert L. Strausberg; Andrew J. Simpson; Kunle O. Odunsi

doi:10.1593/tlo.09199

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

Tanja Pejovic, Nupur T. Pande, Motomi Mori, Paulette Mhawech-Fauceglia, Christina Harrington, Solange Mongoue-Tchokote, Daniel Dim, Christopher Andrews, Amy Beck, Yukie Tarumi, Jovana Djilas, Fabio Cappuccini, Otavia Caballero, Jiaqi Huang, Samuel Levy, Alexia Tsiamouri, Joanna Cain, Grover C. Bagby, Robert L. Strausberg, Andrew J. SimpsonKunle O. Odunsi

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	341-349
Number of pages	9
Journal	Translational Oncology
Volume	2
Issue number	4
DOIs	https://doi.org/10.1593/tlo.09199
State	Published - 2009

ASJC Scopus subject areas

Oncology
Cancer Research

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Pejovic, T., Pande, N. T., Mori, M., Mhawech-Fauceglia, P., Harrington, C., Mongoue-Tchokote, S., Dim, D., Andrews, C., Beck, A., Tarumi, Y., Djilas, J., Cappuccini, F., Caballero, O., Huang, J., Levy, S., Tsiamouri, A., Cain, J., Bagby, G. C., Strausberg, R. L., ... Odunsi, K. O. (2009). Expression profiling of the ovarian surface kinome reveals candidate genes for early neoplastic changes. Translational Oncology, 2(4), 341-349. https://doi.org/10.1593/tlo.09199

Pejovic, T, Pande, NT, Mori, M, Mhawech-Fauceglia, P, Harrington, C, Mongoue-Tchokote, S, Dim, D, Andrews, C, Beck, A, Tarumi, Y, Djilas, J, Cappuccini, F, Caballero, O, Huang, J, Levy, S, Tsiamouri, A, Cain, J, Bagby, GC, Strausberg, RL, Simpson, AJ & Odunsi, KO 2009, 'Expression profiling of the ovarian surface kinome reveals candidate genes for early neoplastic changes', Translational Oncology, vol. 2, no. 4, pp. 341-349. https://doi.org/10.1593/tlo.09199

@article{b46fdbcd08a3447ca3e5458be974bedf,

title = "Expression profiling of the ovarian surface kinome reveals candidate genes for early neoplastic changes",

abstract = "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.",

author = "Tanja Pejovic and Pande, {Nupur T.} and Motomi Mori and Paulette Mhawech-Fauceglia and Christina Harrington and Solange Mongoue-Tchokote and Daniel Dim and Christopher Andrews and Amy Beck and Yukie Tarumi and Jovana Djilas and Fabio Cappuccini and Otavia Caballero and Jiaqi Huang and Samuel Levy and Alexia Tsiamouri and Joanna Cain and Bagby, {Grover C.} and Strausberg, {Robert L.} and Simpson, {Andrew J.} and Odunsi, {Kunle O.}",

note = "Funding Information: Address all correspondence to: Dr. Tanja Pejovic, Gynecologic Oncology, Oregon Health & Science University, L466, 3181 SW Sam Jackson Park Rd, Portland, OR 97239. E-mail: pejovict@ohsu.edu or Dr. Kunle Odunsi, Gynecologic Oncology, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263. 1The study was supported by the Cancer Research Institute{\textquoteright}s Ovarian Cancer Working Group Grant (K.O. and A.J.S.) and the Hilton-Ludwig Cancer Metastasis Grant of the Ludwig Institute for Cancer Research (K.O. and T.P.), grant support from the Department of Veterans Affairs and National Institutes of Health (HL72321 and HL048546) (G.C.B.), the Reproductive Malignancies Program of the Oregon Health & Science University Cancer Institute, Mr. and Mrs. Richard A. Rubinstein, the Sherrie Hildreth Ovarian Cancer Foundation, and the Columbia River Yacht Club. 2This article refers to supplementary materials, which are designated by Tables W1 to W3 and are available online at www.transonc.com. Received 28 July 2009; Revised 24 August 2009; Accepted 28 August 2009 Copyright {\textcopyright} 2009 Neoplasia Press, Inc.OpenaccessunderCCBY-NC-ND license. 1944-7124 DOI 10.1593/tlo.09199",

year = "2009",

doi = "10.1593/tlo.09199",

language = "English (US)",

volume = "2",

pages = "341--349",

journal = "Translational Oncology",

issn = "1944-7124",

publisher = "Neoplasia Press",

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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.

N1 - Funding Information: Address all correspondence to: Dr. Tanja Pejovic, Gynecologic Oncology, Oregon Health & Science University, L466, 3181 SW Sam Jackson Park Rd, Portland, OR 97239. E-mail: pejovict@ohsu.edu or Dr. Kunle Odunsi, Gynecologic Oncology, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263. 1The study was supported by the Cancer Research Institute’s Ovarian Cancer Working Group Grant (K.O. and A.J.S.) and the Hilton-Ludwig Cancer Metastasis Grant of the Ludwig Institute for Cancer Research (K.O. and T.P.), grant support from the Department of Veterans Affairs and National Institutes of Health (HL72321 and HL048546) (G.C.B.), the Reproductive Malignancies Program of the Oregon Health & Science University Cancer Institute, Mr. and Mrs. Richard A. Rubinstein, the Sherrie Hildreth Ovarian Cancer Foundation, and the Columbia River Yacht Club. 2This article refers to supplementary materials, which are designated by Tables W1 to W3 and are available online at www.transonc.com. Received 28 July 2009; Revised 24 August 2009; Accepted 28 August 2009 Copyright © 2009 Neoplasia Press, Inc.OpenaccessunderCCBY-NC-ND license. 1944-7124 DOI 10.1593/tlo.09199

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.

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

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