Expression of young HERV-H loci in the course of colorectal carcinoma and correlation with molecular subtypes
2015
Pérot, Philippe | Mullins, Christina, Susanne | Naville, Magali | Bressan, Cédric | Hühns, Maja | Gock, Michael | Kühn, Florian | Volff, Jean-Nicolas | Trillet-Lenoir, Véronique | Linnebacher, Michael | Mallet, François | Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS) ; Hospices Civils de Lyon (HCL) | BIOMERIEUX [Lyon, France] | Ciblage thérapeutique en Oncologie (EA3738) ; Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon | Institut de Génomique Fonctionnelle de Lyon (IGFL) ; École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Centre National de la Recherche Scientifique (CNRS) | University of Rostock = Universität Rostock | CSM received a “Mildred Scheel PostDoc Stipendium” from the German Cancer Aid (DKH e.V. #110943). This work was supported by bioMérieux SA and the French public agency OSEO (Advanced Diagnostics for New Therapeutic Approaches, a French government-funded program dedicated to personalized medicine) and by the German Cancer Aid Foundation (DKH e.V. #108446).
International audience
اظهر المزيد [+] اقل [-]إنجليزي. 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.
اظهر المزيد [+] اقل [-]المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل Institut national de la recherche agronomique