Differences in cancer gene copy number alterations between Epstein-Barr virus-positive and Epstein-Barr virus-negative nasopharyngeal carcinoma

Marc Lucas Ooft; Jolique van Ipenburg; Rob J.M. van de Loo; Rick de Jong; Cathy B. Moelans; Remco de Bree; Martine J. de Herdt; Senada Koljenović; R. Baatenburg de Jong; J. Hardillo; Stefan Martin Willems

doi:10.1002/hed.25195

Differences in cancer gene copy number alterations between Epstein-Barr virus-positive and Epstein-Barr virus-negative nasopharyngeal carcinoma

Marc Lucas Ooft, Jolique van Ipenburg, Rob J.M. van de Loo, Rick de Jong, Cathy B. Moelans, Remco de Bree, Martine J. de Herdt, Senada Koljenović, R. Baatenburg de Jong, J. Hardillo, Stefan Martin Willems^*

^*Corresponding author for this work

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

Abstract

Background: Nasopharyngeal carcinoma (NPC) treatment is mainly based on clinical staging. We hypothesize that better understanding of the molecular heterogeneity of NPC can aid in better treatment decisions. Therefore, the purpose of this study was to present our exploration of cancer gene copy-number alterations (CNAs) of Epstein-Barr virus (EBV)-positive and EBV-negative NPC. Methods: Multiplex ligation-dependent probe amplification was applied to detect CNAs of 36 cancer genes (n = 103). Correlation between CNAs, clinicopathological features, and survival were examined. Results: The CNAs occurred significantly more in EBV-negative NPC, with PIK3CA and MCCC1 (P <.001) gain/amplification occurring more frequently. Gain/amplification of cyclin-L1 (CCNL1) and PTK2 (P <.001) predict worse disease-free survival (DFS) in EBV-positive NPC. Conclusion: The EBV-positive and EBV-negative NPC show some similarities in cancer gene CNAs suggesting a common pathogenic route but also important differences possibly indicating divergence in oncogenesis. Copy number gain/amplification of CCNL1 and PTK2 are possibly good predictors of survival in EBV-positive NPC.

Original language	English
Pages (from-to)	1986-1998
Number of pages	13
Journal	Head & neck
Volume	40
Issue number	9
DOIs	https://doi.org/10.1002/hed.25195
Publication status	Published - 1 Sept 2018

Keywords

Epstein-Barr virus
copy-number alterations
gene
multiplex ligation-dependent probe amplification
nasopharyngeal carcinoma

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10.1002/hed.25195

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Ooft, M. L., van Ipenburg, J., van de Loo, R. J. M., de Jong, R., Moelans, C. B., de Bree, R., de Herdt, M. J., Koljenović, S., de Jong, R. B., Hardillo, J., & Willems, S. M. (2018). Differences in cancer gene copy number alterations between Epstein-Barr virus-positive and Epstein-Barr virus-negative nasopharyngeal carcinoma. Head & neck, 40(9), 1986-1998. https://doi.org/10.1002/hed.25195

@article{9c0114f4cf5f4bb1a1c72355d83e64bf,

title = "Differences in cancer gene copy number alterations between Epstein-Barr virus-positive and Epstein-Barr virus-negative nasopharyngeal carcinoma",

abstract = "Background: Nasopharyngeal carcinoma (NPC) treatment is mainly based on clinical staging. We hypothesize that better understanding of the molecular heterogeneity of NPC can aid in better treatment decisions. Therefore, the purpose of this study was to present our exploration of cancer gene copy-number alterations (CNAs) of Epstein-Barr virus (EBV)-positive and EBV-negative NPC. Methods: Multiplex ligation-dependent probe amplification was applied to detect CNAs of 36 cancer genes (n = 103). Correlation between CNAs, clinicopathological features, and survival were examined. Results: The CNAs occurred significantly more in EBV-negative NPC, with PIK3CA and MCCC1 (P <.001) gain/amplification occurring more frequently. Gain/amplification of cyclin-L1 (CCNL1) and PTK2 (P <.001) predict worse disease-free survival (DFS) in EBV-positive NPC. Conclusion: The EBV-positive and EBV-negative NPC show some similarities in cancer gene CNAs suggesting a common pathogenic route but also important differences possibly indicating divergence in oncogenesis. Copy number gain/amplification of CCNL1 and PTK2 are possibly good predictors of survival in EBV-positive NPC.",

keywords = "Epstein-Barr virus, copy-number alterations, gene, multiplex ligation-dependent probe amplification, nasopharyngeal carcinoma",

author = "Ooft, \{Marc Lucas\} and \{van Ipenburg\}, Jolique and \{van de Loo\}, \{Rob J.M.\} and \{de Jong\}, Rick and Moelans, \{Cathy B.\} and \{de Bree\}, Remco and \{de Herdt\}, \{Martine J.\} and Senada Koljenovi{\'c} and \{de Jong\}, \{R. Baatenburg\} and J. Hardillo and Willems, \{Stefan Martin\}",

note = "Publisher Copyright: {\textcopyright} 2018 Wiley Periodicals, Inc.",

year = "2018",

month = sep,

day = "1",

doi = "10.1002/hed.25195",

language = "English",

volume = "40",

pages = "1986--1998",

journal = "Head \& neck",

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Ooft, ML, van Ipenburg, J, van de Loo, RJM, de Jong, R, Moelans, CB , de Bree, R, de Herdt, MJ, Koljenović, S, de Jong, RB, Hardillo, J & Willems, SM 2018, 'Differences in cancer gene copy number alterations between Epstein-Barr virus-positive and Epstein-Barr virus-negative nasopharyngeal carcinoma', Head & neck, vol. 40, no. 9, pp. 1986-1998. https://doi.org/10.1002/hed.25195

TY - JOUR

T1 - Differences in cancer gene copy number alterations between Epstein-Barr virus-positive and Epstein-Barr virus-negative nasopharyngeal carcinoma

AU - Ooft, Marc Lucas

AU - van Ipenburg, Jolique

AU - van de Loo, Rob J.M.

AU - de Jong, Rick

AU - Moelans, Cathy B.

AU - de Bree, Remco

AU - de Herdt, Martine J.

AU - Koljenović, Senada

AU - de Jong, R. Baatenburg

AU - Hardillo, J.

AU - Willems, Stefan Martin

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background: Nasopharyngeal carcinoma (NPC) treatment is mainly based on clinical staging. We hypothesize that better understanding of the molecular heterogeneity of NPC can aid in better treatment decisions. Therefore, the purpose of this study was to present our exploration of cancer gene copy-number alterations (CNAs) of Epstein-Barr virus (EBV)-positive and EBV-negative NPC. Methods: Multiplex ligation-dependent probe amplification was applied to detect CNAs of 36 cancer genes (n = 103). Correlation between CNAs, clinicopathological features, and survival were examined. Results: The CNAs occurred significantly more in EBV-negative NPC, with PIK3CA and MCCC1 (P <.001) gain/amplification occurring more frequently. Gain/amplification of cyclin-L1 (CCNL1) and PTK2 (P <.001) predict worse disease-free survival (DFS) in EBV-positive NPC. Conclusion: The EBV-positive and EBV-negative NPC show some similarities in cancer gene CNAs suggesting a common pathogenic route but also important differences possibly indicating divergence in oncogenesis. Copy number gain/amplification of CCNL1 and PTK2 are possibly good predictors of survival in EBV-positive NPC.

AB - Background: Nasopharyngeal carcinoma (NPC) treatment is mainly based on clinical staging. We hypothesize that better understanding of the molecular heterogeneity of NPC can aid in better treatment decisions. Therefore, the purpose of this study was to present our exploration of cancer gene copy-number alterations (CNAs) of Epstein-Barr virus (EBV)-positive and EBV-negative NPC. Methods: Multiplex ligation-dependent probe amplification was applied to detect CNAs of 36 cancer genes (n = 103). Correlation between CNAs, clinicopathological features, and survival were examined. Results: The CNAs occurred significantly more in EBV-negative NPC, with PIK3CA and MCCC1 (P <.001) gain/amplification occurring more frequently. Gain/amplification of cyclin-L1 (CCNL1) and PTK2 (P <.001) predict worse disease-free survival (DFS) in EBV-positive NPC. Conclusion: The EBV-positive and EBV-negative NPC show some similarities in cancer gene CNAs suggesting a common pathogenic route but also important differences possibly indicating divergence in oncogenesis. Copy number gain/amplification of CCNL1 and PTK2 are possibly good predictors of survival in EBV-positive NPC.

KW - Epstein-Barr virus

KW - copy-number alterations

KW - gene

KW - multiplex ligation-dependent probe amplification

KW - nasopharyngeal carcinoma

UR - https://www.scopus.com/pages/publications/85053011531

U2 - 10.1002/hed.25195

DO - 10.1002/hed.25195

M3 - Article

C2 - 29927011

SN - 1043-3074

VL - 40

SP - 1986

EP - 1998

JO - Head & neck

JF - Head & neck

IS - 9

ER -

Differences in cancer gene copy number alterations between Epstein-Barr virus-positive and Epstein-Barr virus-negative nasopharyngeal carcinoma

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Keywords

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