title: Expression of young HERV-H loci in the course of colorectal carcinoma and correlation with molecular subtypes.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cancer Biomarkers Research Group, Joint Unit Hospices Civils de Lyon, bioMérieux, Centre Hospitalier Lyon Sud, Pierre Bénite, France.|Current address: Institut Pasteur, Laboratory for Pathogen Discovery, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pérot
authors.affiliation: Cancer Biomarkers Research Group, Joint Unit Hospices Civils de Lyon, bioMérieux, Centre Hospitalier Lyon Sud, Pierre Bénite, France.|Centre d'Investigation des Thérapeutiques en Oncologie et Hématologie, EMR 3738 Lyon Claude Bernard University, Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France.
authors.forename: Christina Susanne
authors.initials: CS
authors.lastname: Mullins
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure de Lyon, CNRS/Université Lyon I, Lyon, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Naville
authors.affiliation: Cancer Biomarkers Research Group, Joint Unit Hospices Civils de Lyon, bioMérieux, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Bressan
authors.affiliation: Institute of Pathology, University Medicine Rostock, Rostock, Germany.
authors.forename: Maja
authors.initials: M
authors.lastname: Hühns
authors.affiliation: Department of General, Thoracic, Vascular and Transplantation Surgery, University Medicine Rostock, Rostock, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gock
authors.affiliation: Department of General, Thoracic, Vascular and Transplantation Surgery, University Medicine Rostock, Rostock, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Kühn
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure de Lyon, CNRS/Université Lyon I, Lyon, France.
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Volff
authors.affiliation: Centre d'Investigation des Thérapeutiques en Oncologie et Hématologie, EMR 3738 Lyon Claude Bernard University, Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Trillet-Lenoir
authors.affiliation: Department of General Surgery, Molecular Oncology and Immunotherapy, University Medicine Rostock, Rostock, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebacher
authors.affiliation: Cancer Biomarkers Research Group, Joint Unit Hospices Civils de Lyon, bioMérieux, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
authors.forename: François
authors.initials: F
authors.lastname: Mallet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D018450:Disease Progression; D020077:Endogenous Retroviruses / Q000145:classification / Q000235:genetics* / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral / Q000235:genetics; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D020079:Terminal Repeat Sequences / Q000235:genetics; D055815:Young Adult
keywords: HERV-H; biomarker; colorectal cancer; microsatellite instability; qRT-PCR