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© Therese Couderc, Marc Lecuit
Publication : Oncotarget

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Oncotarget - 24 Nov 2015

Pérot P, Mullins CS, Naville M, Bressan C, Hühns M, Gock M, Kühn F, Volff JN, Trillet-Lenoir V, Linnebacher M, Mallet F

Link to Pubmed [PMID] – 26517682

Oncotarget 2015 Nov;6(37):40095-111

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.

https://www.ncbi.nlm.nih.gov/pubmed/26517682