Oncotarget

Research Papers:

Expression of young HERV-H loci in the course of colorectal carcinoma and correlation with molecular subtypes

Philippe Pérot _, Christina Susanne Mullins, Magali Naville, Cédric Bressan, Maja Hühns, Michael Gock, Florian Kühn, Jean-Nicolas Volff, Véronique Trillet-Lenoir, Michael Linnebacher, François Mallet

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Oncotarget. 2015; 6:40095-40111. https://doi.org/10.18632/oncotarget.5539

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Abstract

Philippe Pérot1,7,*, Christina Susanne Mullins1,2,*, Magali Naville3, Cédric Bressan1, Maja Hühns4, Michael Gock5, Florian Kühn5, Jean-Nicolas Volff3, Véronique Trillet-Lenoir2, Michael Linnebacher6,*, François Mallet1,*

1Cancer Biomarkers Research Group, Joint Unit Hospices Civils de Lyon, bioMérieux, Centre Hospitalier Lyon Sud, Pierre Bénite, France

2Centre d’Investigation des Thérapeutiques en Oncologie et Hématologie, EMR 3738 Lyon Claude Bernard University, Institut de Cancérologie des Hospices Civils de Lyon, France

3Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure de Lyon, CNRS/Université Lyon I, Lyon, France

4Institute of Pathology, University Medicine Rostock, Rostock, Germany

5Department of General, Thoracic, Vascular and Transplantation Surgery, University Medicine Rostock, Rostock, Germany

6Department of General Surgery, Molecular Oncology and Immunotherapy, University Medicine Rostock, Rostock, Germany

7Current address: Institut Pasteur, Laboratory for Pathogen Discovery, Paris, France

*These authors have contributed equally to this work

Correspondence to:

Michael Linnebacher, e-mail: michael.linnebacher@med.uni-rostock.de

François Mallet, e-mail: francois.mallet@biomerieux.com

Keywords: colorectal cancer, HERV-H, microsatellite instability, qRT-PCR, biomarker

Received: June 28, 2015     Accepted: October 13, 2015     Published: October 23, 2015

ABSTRACT

Background: Expression of the human endogenous retrovirus (HERV)-H family has been associated with colorectal carcinomas (CRC), yet no individual HERV-H locus expression has been thoroughly correlated with clinical data.

Here, we characterized HERV-H reactivations in clinical CRC samples by integrating expression profiles, molecular patterns and clinical data. Expression of relevant HERV-H sequences was analyzed by qRT-PCR on two well-defined clinical cohorts (n = 139 pairs of tumor and adjacent normal colon tissue) including samples from adenomas (n = 21) and liver metastases (n = 16). Correlations with clinical and molecular data were assessed.

Results: CRC specific HERV-H sequences were validated and found expressed throughout CRC disease progression. Correlations between HERV-H expression and lymph node invasion of tumor cells (p = 0.0006) as well as microsatellite instable tumors (p < 0.0001) were established. No association with regard to age, tumor localization, grading or common mutations became apparent. Interestingly, CRC expressed elements belonged to specific young HERV-H subfamilies and their 5′ LTR often presented active histone marks.

Conclusion: These results suggest a functional role of HERV-H sequences in colorectal carcinogenesis. The pronounced connection with microsatellite instability warrants a more detailed investigation. Thus, HERV-H sequences in addition to tumor specific mutations may represent clinically relevant, truly CRC specific markers for diagnostic, prognostic and therapeutic purposes.

Author Information

Philippe Pérot
Primary Contact  _

Christina Susanne Mullins

Magali Naville

Cédric Bressan

Maja Hühns

Michael Gock

Florian Kühn

Jean-Nicolas Volff

Véronique Trillet-Lenoir

Michael Linnebacher

François Mallet


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