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Transcription from a gene desert in a melanoma porcine model

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Abstract

The genetic mechanisms underlying cutaneous melanoma onset and progression need to be further understood to improve patients’ care. Several studies have focused on the genetic determinism of melanoma development in the MeLiM pig, a biomedical model of cutaneous melanoma. The objective of this study was to better describe the influence of a particular genomic region on melanoma progression in the MeliM model. Indeed, a large region of the Sus scrofa chromosome 1 has been identified by linkage and association analyses, but the causal mechanisms have remained elusive. To deepen the analysis of this candidate region, a dedicated SNP panel was used to fine map the locus, downsizing the interval to less than 2 Mb, in a genomic region located within a large gene desert. Transcription from this locus was addressed using a tiling array strategy and further validated by RT-PCR in a large panel of tissues. Overall, the gene desert showed an extensive transcriptional landscape, notably dominated by repeated element transcription in tumor and fetal tissues. The transcription of LINE-1 and PERVs has been confirmed in skin and tumor samples from MeLiM pigs. In conclusion, although this study still does not identify a candidate mutation for melanoma occurrence or progression, it highlights a potential role of repeated element transcriptional activity in the MeLiM model.

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Acknowledgements

This work was funded by the French National Research Agency (ANR PSC-08-GENO-CapSeqAn), La Ligue Nationale Contre le Cancer (Genetic Epidemiology PRE09/FD), INCa (PL-Bio 5982), and regular funding from CEA (Commissariat à l’Energie Atomique et aux Energies Alternatives) and INRA (Institut National de la Recherche Agronomique). J. Estellé was funded by the INRA program ‘Jeunes Docteurs’ and A. Blin fellowship was funded by La Ligue contre le cancer. The authors wish to acknowledge the staff involved in animal management and phenotyping, as well as Dr Denis Milan and Sigenae staff for help with providing SNP information from initial sequencing programs conducted in pigs.

Funding

This study was funded by the French National Research Agency (ANR PSC-08-GENO-CapSeqAn), La Ligue Nationale Contre le Cancer (Genetic Epidemiology PRE09/FD), INCa (PL-Bio 5982), and regular funding from CEA (Commissariat à l’Energie Atomique et aux Energies Alternatives) and INRA (Institut National de la Recherche Agronomique). J. Estellé was funded by the INRA program ‘Jeunes Docteurs’ and A. Blin fellowship was funded by La Ligue contre le cancer.

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Performed data analysis: SM, JE, AB, PW, EB. Performed experiments: FC, JL, FT. Secured funding and initiated the project: EB, CR-G. Supervised: EB. Wrote the manuscript: EB.

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Correspondence to E. Bourneuf.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The animal facility is under license issued by the Direction Départementale de la protection des populations des Yvelines (agreement number DDPP-VET-16-000146) and experiments were ethically approved by the Committee on the Ethics of Animal Experiments of AgroParisTech and INRA Jouy-en-Josas (COMETHEA, authorization number 12/091). This article does not contain any studies with human participants performed by any of the authors.

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Marthey, S., Estellé, J., Blin, A. et al. Transcription from a gene desert in a melanoma porcine model. Mol Genet Genomics 295, 1239–1252 (2020). https://doi.org/10.1007/s00438-020-01694-6

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