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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Akbani R, Akdemir KC, Aksoy BA, Albert M, Ally A, Amin SB, Arachchi H, Arora A, Auman JT, Ayala B, Baboud J, Balasundaram M, Balu S, Barnabas N, Bartlett J, Bartlett P, Bastian BC, Baylin SB, Behera M, Belyaev D, Benz C, Bernard B, Beroukhim R, Bir N, Black AD, Bodenheimer T, Boice L, Boland GM, Bono R et al (2015) Genomic classification of cutaneous melanoma. Cell 161:1681–1696
Balestrieri E, Argaw-Denboba A, Gambacurta A, Cipriani C, Bei R, Serafino A, Sinibaldi-Vallebona P, Matteucci C (2018) Human endogenous retrovirus K in the crosstalk between cancer cells microenvironment and plasticity: a new perspective for combination therapy. Front Microbiol 9:1448. https://doi.org/10.3389/fmicb.2018.01448
Bolstad BM, Irizarry RA, Astrand M, Speed TP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19:185–193
Bourneuf E (2017) The MeLiM minipig: an original spontaneous model to explore cutaneous melanoma genetic basis. Front Genet 8:146. https://doi.org/10.3389/fgene.2017.00146
Bourneuf E, Du Z-Q, Estellé J, Gilbert H, Créchet F, Piton G, Milan D, Geffrotin C, Lathrop M, Demenais F, Rogel-Gaillard C, Vincent-Naulleau S (2011) Genetic and functional evaluation of MITF as a candidate gene for cutaneous melanoma predisposition in pigs. Mamm Genome 22:602–612
Bourneuf E, Estellé J, Blin A, Créchet F, Schneider MDP, Gilbert H, Brossard M, Vaysse A, Lathrop M, Vincent-Naulleau S, Demenais F (2018) New susceptibility loci for cutaneous melanoma risk and progression revealed using a porcine model. Oncotarget 9:27682–27697. https://doi.org/10.18632/oncotarget.25455
Cañadas I, Thummalapalli R, Kim JW, Kitajima S, Jenkins RW, Christensen CL, Campisi M, Kuang Y, Zhang Y, Gjini E, Zhang G, Tian T, Sen DR, Miao D, Imamura Y, Thai T, Piel B, Terai H, Aref AR, Hagan T, Koyama S, Watanabe M, Baba H, Adeni AE, Lydon CA, Tamayo P, Wei Z, Herlyn M, Barbie TU, Uppaluri R, Sholl LM, Sicinska E, Sands J, Rodig S, Wong KK, Paweletz CP, Watanabe H, Barbie DA (2018) Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses. Nat Med 24:1143–1150
Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C, Akman B, Hein A, Rote NS, Cope LM, Snyder A, Makarov V, Buhu S, Slamon DJ, Wolchok JD, Pardoll DM, Beckmann MW, Zahnow CA, Mergoub T, Chan TA, Baylin SB, Strick R (2015) Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162:974–986
Choi Y, Nam J, Whitcomb DJ, Song YS, Kim D, Jeon S, Um JW, Lee S-G, Woo J, Kwon S-K, Li Y, Mah W, Kim HM, Ko J, Cho K, Kim E (2016) SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development. Sci Rep 6:26676
Chuong EB, Elde NC, Feschotte C (2016) Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science 351:1083–1087
David L, Clauder-Münster S, Steinmetz LM (2011) Genome-wide transcriptome analysis in yeast using high-density tiling arrays. In: Castrillo JI, Oliver SG (eds) Yeast systems biology. Humana Press, Totowa, pp 107–123
Denner J (2016) How active are porcine endogenous retroviruses (PERVs)? Viruses 8(8):215. https://doi.org/10.3390/v8080215
Denner J (2018) Why was PERV not transmitted during preclinical and clinical xenotransplantation trials and after inoculation of animals? Retrovirology 15(1):28
Dieckhoff B, Puhlmann J, Büscher K, Hafner-Marx A, Herbach N, Bannert N, Büttner M, Wanke R, Kurth R, Denner J (2007) Expression of porcine endogenous retroviruses (PERVs) in melanomas of Munich miniature swine (MMS) Troll. Veterinary Microbiol 123:53–68. https://doi.org/10.1016/jvetmic200702024
Du Z-Q, Vincent-Naulleau S, Gilbert H, Vignoles F, Créchet F, Shimogiri T, Yasue H, Leplat J-J, Bouet S, Gruand J, Horak V, Milan D, Le Roy P, Geffrotin C (2007) Detection of novel quantitative trait loci for cutaneous melanoma by genome-wide scan in the MeLiM swine model. Int J Cancer 120:303–320
Faulkner GJ, Billon V (2018) L1 retrotransposition in the soma: a field jumping ahead. Mobile DNA 9:22. https://doi.org/10.1186/s13100-018-0128-1
Faulkner GJ, Kimura Y, Daub CO, Wani S, Plessy C, Irvine KM, Schroder K, Cloonan N, Steptoe AL, Lassmann T, Waki K, Hornig N, Arakawa T, Takahashi H, Kawai J, Forrest ARR, Suzuki H, Hayashizaki Y, Hume DA, Orlando V, Grimmond SM, Carninci P (2009a) The regulated retrotransposon transcriptome of mammalian cells. Nat Genet 41:563–571. https://doi.org/10.1038/ng.368
Faulkner GJ, Kimura Y, Daub CO, Wani S, Plessy C, Irvine KM, Schroder K, Cloonan N, Steptoe AL, Lassmann T, Waki K, Hornig N, Arakawa T, Takahashi H, Kawai J, Forrest ARR, Suzuki H, Hayashizaki Y, Hume DA, Orlando V, Grimmond SM, Carninci P (2009b) The regulated retrotransposon transcriptome of mammalian cells. Nat Genet 41:563–571. https://doi.org/10.1038/ng.368
Fiebig U, Fischer K, Bähr A, Runge C, Schnieke A, Wolf E, Denner J (2018) Porcine endogenous retroviruses: quantification of the copy number in cell lines pig breeds and organs. Xenotransplantation 25:e12445. https://doi.org/10.1111/xen12445
Flood WD, Moyer RW, Tsykin A, Sutherland GR, Koblar SA (2004) Nxf and Fbxo33: novel seizure-responsive genes in mice. Eur J Neurosci 20:1819–1826
Geffrotin C, Crechet F, Le Roy P, Le Chalony C, Leplat J-J, Iannuccelli N, Barbosa A, Renard C, Gruand J, Milan D, Horak V, Tricaud Y, Bouet S, Franck M, Frelat G, Vincent-Naulleau S (2004) Identification of five chromosomal regions involved in predisposition to melanoma by genome-wide scan in the MeLiM swine model. Int J Cancer 110:39–50
Giuffra E, Tuggle CK, FAANG Consortium (2019) Functional annotation of animal genomes (FAANG): current achievements and roadmap. Annu Rev Anim Biosci 7:65–88
Godehardt AW, Petkov S, Gulich B, Fischer N, Niemann H, Tönjes RR (2018) Comparative gene expression profiling of pig-derived iPSC-like cells: effects of induced pluripotency on expression of porcine endogenous retrovirus (PERV). Xenotransplantation 25(4):e12429
Gong J, Li Y, Liu C, Xiang Y, Li C, Ye Y, Zhang Z, Hawke DH, Park PK, Diao L, Putkey JA, Yang L, Guo A-Y, Lin C, Han L (2017) A pan-cancer analysis of the expression and clinical relevance of small nucleolar RNAs in human cancer. Cell Rep 21:1968–1981
Grandi N, Tramontano E (2018) Human endogenous retroviruses are ancient acquired elements still shaping innate immune responses. Front Immunol 9:2039. https://doi.org/10.3389/fimmu201802039
Groenen MAM, Archibald AL, Uenishi H, Tuggle CK, Takeuchi Y, Rothschild MF, Rogel-Gaillard C, Park C, Milan D, Megens H-J, Li S, Larkin DM, Kim H, Frantz LAF, Caccamo M, Ahn H, Aken BL, Anselmo A, Anthon C, Auvil L, Badaoui B, Beattie CW, Bendixen C, Berman D, Blecha F, Blomberg J, Bolund L, Bosse M et al (2012) Analyses of pig genomes provide insight into porcine demography and evolution. Nature 491:393–398. https://doi.org/10.1038/nature11622
Hoshimoto S, Kuo CT, Chong KK, Takeshima T-L, Takei Y, Li MW, Huang SK, Sim M-S, Morton DL, Hoon DSB (2012) AIM1 and LINE-1 epigenetic aberrations in tumor and serum relate to melanoma progression and disease outcome. J Investig Dermatol 132:1689–1697
Humphray SJ, Scott CE, Clark R, Marron B, Bender C, Camm N, Davis J, Jenks A, Noon A, Patel M, Sehra H, Yang F, Rogatcheva MB, Milan D, Chardon P, Rohrer G, Nonneman D, de Jong P, Meyers SN, Archibald A, Beever JE, Schook LB, Rogers J (2007) A high utility integrated map of the pig genome. Genome Biol 8:R139. https://doi.org/10.1186/gb-2007-8-7-r139
Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, Barrette TR, Prensner JR, Evans JR, Zhao S, Poliakov A, Cao X, Dhanasekaran SM, Wu Y-M, Robinson DR, Beer DG, Feng FY, Iyer HK, Chinnaiyan AM (2015) The landscape of long noncoding RNAs in the human transcriptome. Nat Genet 47:199
Johnson JM, Edwards S, Shoemaker D, Schadt EE (2005) Dark matter in the genome: evidence of widespread transcription detected by microarray tiling experiments. Trends Genet 21:93–102. https://doi.org/10.1016/jtig200412009
Julé S, Bossé P, Egidy G, Panthier J-J (2003) Establishment and characterization of a normal melanocyte cell line derived from pig skin. Pigment Cell Res 16:407–410
Ling H, Vincent K, Pichler M, Fodde R, Berindan-Neagoe I, Slack FJ, Calin GA (2015) Junk DNA and the long non-coding RNA twist in cancer genetics. Oncogene 34:5003–5011
Liu G, Li Z, Pan M, Ge M, Wang Y, Gao Y (2011) Genetic prevalence of porcine endogenous retrovirus in chinese experimental miniature pigs. Transplant Proc 43(7):2762–2769
Łopata K, Wojdas E, Nowak R, Łopata P, Mazurek U (2018) Porcine endogenous retrovirus (PERV)—molecular structure and replication strategy in the context of retroviral infection risk of human cells. Front Microbiol 9:730
Mavragani CP, Sagalovskiy I, Guo Q, Nezos A, Kapsogeorgou EK, Lu P, Liang Zhou J, Kirou KA, Seshan SV, Moutsopoulos HM, Crow MK (2016) Expression of long interspersed nuclear element 1 retroelements and induction of type i interferon in patients with systemic autoimmune disease. Arthritis Rheumatol (Hoboken NJ) 68:2686–2696
Moarii M, Boeva V, Vert J-P, Reyal F (2015) Changes in correlation between promoter methylation and gene expression in cancer. BMC Genomics 16:873. https://doi.org/10.1186/s12864-015-1994-2
Naumova OY, Lee M, Rychkov SY, Vlasova NV, Grigorenko EL (2013) Gene expression in the human brain: the current state of the study of specificity and spatiotemporal dynamics. Child Dev 84:76–88
Ovcharenko I, Loots GG, Nobrega MA, Hardison RC, Miller W, Stubbs L (2005) Evolution and functional classification of vertebrate gene deserts. Genome Res 15:137–145
Papasotiriou I, Pantopikou K, Apostolou P (2017) L1 retrotransposon expression in circulating tumor cells. PLoS ONE 12:e0171466. https://doi.org/10.1371/journalpone0171466
Pérez-Enciso M, Misztal I (2004) Qxpak: a versatile mixed model application for genetical genomics and QTL analyses. Bioinformatics 20:2792–2798. https://doi.org/10.1093/bioinformatics/bth331
Picard F, Robin S, Lavielle M, Vaisse C, Daudin J-J (2005) A statistical approach for array CGH data analysis. BMC Bioinf 6:27. https://doi.org/10.1186/1471-2105-6-27
Prensner JR, Iyer MK, Balbin OA, Dhanasekaran SM, Cao Q, Brenner JC, Laxman B, Asangani IA, Grasso CS, Kominsky HD, Cao X, Jing X, Wang X, Siddiqui J, Wei JT, Robinson D, Iyer HK, Palanisamy N, Maher CA, Chinnaiyan AM (2011) Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1 an unannotated lincRNA implicated in disease progression. Nat Biotechnol 29:742–749
Rambow F, Piton G, Bouet S, Leplat J-J, Baulande S, Marrau A, Stam M, Horak V, Vincent-Naulleau S (2008) Gene expression signature for spontaneous cancer regression in melanoma pigs. Neoplasia 10:714–726 (1 p following 726)
Ramsköld D, Wang ET, Burge CB, Sandberg R (2009) An abundance of ubiquitously expressed genes revealed by tissue transcriptome sequence data. PLoS Comput Biol 5:e1000598. https://doi.org/10.1371/journalpcbi1000598
Rodić N, Sharma R, Sharma R, Zampella J, Dai L, Taylor MS, Hruban RH, Iacobuzio-Donahue CA, Maitra A, Torbenson MS, Goggins M, Shih I-M, Duffield AS, Montgomery EA, Gabrielson E, Netto GJ, Lotan TL, De Marzo AM, Westra W, Binder ZA, Orr BA, Gallia GL, Eberhart CG, Boeke JD, Harris CR, Burns KH (2014) Long interspersed element-1 protein expression is a hallmark of many human cancers. Am J Pathol 184:1280–1286
Roulois D, Loo Yau H, Singhania R, Wang Y, Danesh A, Shen SY, Han H, Liang G, Jones PA, Pugh TJ, O’Brien C, De Carvalho DD (2015) DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 162:961–973
Royce TE, Rozowsky JS, Gerstein MB (2007) Assessing the need for sequence-based normalization in tiling microarray experiments. Bioinformatics 23:988–997. https://doi.org/10.1093/bioinformatics/btm052
Rycaj K, Plummer JB, Yin B, Li M, Garza J, Radvanyi L, Ramondetta LM, Lin K, Johanning GL, Tang DG, Wang-Johanning F (2015) Cytotoxicity of human endogenous retrovirus K-specific T cells toward autologous ovarian cancer cells. Clin Cancer Res 21:471–483
Sanchez-Luque FJ, Kempen M-JHC, Gerdes P, Vargas-Landin DB, Richardson SR, Troskie R-L, Jesuadian JS, Cheetham SW, Carreira PE, Salvador-Palomeque C, García-Cañadas M, Muñoz-Lopez M, Sanchez L, Lundberg M, Macia A, Heras SR, Brennan PM, Lister R, Garcia-Perez JL, Ewing AD, Faulkner GJ (2019) LINE-1 evasion of epigenetic repression in humans. Mol Cell. https://doi.org/10.1016/j.molcel.2019.05.024
Sánchez-Mora C, Ramos-Quiroga JA, Bosch R, Corrales M, Garcia-Martínez I, Nogueira M, Pagerols M, Palomar G, Richarte V, Vidal R, Arias-Vasquez A, Bustamante M, Forns J, Gross-Lesch S, Guxens M, Hinney A, Hoogman M, Jacob C, Jacobsen KK, Kan CC, Kiemeney L, Kittel-Schneider S, Klein M, Onnink M, Rivero O, Zayats T, Buitelaar J, Faraone SV, Franke B, Haavik J, Johansson S, Lesch K-P, Reif A, Sunyer J, Bayés M, Casas M, Cormand B, Ribasés M (2015) Case-control genome-wide association study of persistent attention-deficit hyperactivity disorder identifies FBXO33 as a novel susceptibility gene for the disorder. Neuropsychopharmacology 40:915–926
Scott EC, Gardner EJ, Masood A, Chuang NT, Vertino PM, Devine SE (2016) A hot L1 retrotransposon evades somatic repression and initiates human colorectal cancer. Genome Res 26:745–755
Sinibaldi-Vallebona P, Matteucci C, Spadafora C (2011) Retrotransposon-encoded reverse transcriptase in the genesis progression and cellular plasticity of human cancer. Cancers. https://doi.org/10.3390/cancers3011141
Solyom S, Kazazian HH (2012) Mobile elements in the human genome: implications for disease. Genome Med 4:12. https://doi.org/10.1186/gm311
Sunami E, de Maat M, Vu A, Turner RR, Hoon DSB (2011) LINE-1 hypomethylation during primary colon cancer progression. PLoS ONE 6:e18884. https://doi.org/10.1371/journalpone0018884
The FAANG Consortium, Andersson L, Archibald AL, Bottema CD, Brauning R, Burgess SC, Burt DW, Casas E, Cheng HH, Clarke L, Couldrey C, Dalrymple BP, Elsik CG, Foissac S, Giuffra E, Groenen MA, Hayes BJ, Huang LS, Khatib H, Kijas JW, Kim H, Lunney JK, McCarthy FM, McEwan JC, Moore S, Nanduri B, Notredame C, Palti Y, Plastow GS, Reecy JM, Rohrer GA, Sarropoulou E, Schmidt CJ, Silverstein J, Tellam RL, Tixier-Boichard M, Tosser-Klopp G, Tuggle CK, Vilkki J, White SN, Zhao S, Zhou H (2015) Coordinated international action to accelerate genome-to-phenome with FAANG the Functional Annotation of Animal Genomes project. Genome Biol. https://doi.org/10.1186/s13059-015-0622-4
Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson A, Kampf C, Sjostedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto CA-K, Odeberg J, Djureinovic D, Takanen JO, Hober S, Alm T, Edqvist P-H, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Ponten F (2015) Tissue-based map of the human proteome. Science 347:1260419–1260419
Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D et al (2001) The sequence of the human genome. Science 291:1304–1351. https://doi.org/10.1126/science.1058040
Vincent-Naulleau S, Le Chalony C, Leplat J-J, Bouet S, Bailly C, Spatz A, Vielh P, Avril M-F, Tricaud Y, Gruand J, Horak V, Frelat G, Geffrotin C (2004) Clinical and histopathological characterization of cutaneous melanomas in the melanoblastoma-bearing Libechov minipig model. Pigment Cell Res 17:24–35
Warr A, Affara N, Aken B, Beiki H, Bickhart DM, Billis K, Chow W, Eory L, Finlayson HA, Flicek P, Girón CG, Griffin DK, Hall R, Hannum G, Hourlier T, Howe K, Hume DA, Izuogu O, Kim K, Koren S, Liu H, Manchanda N, Martin FJ, Nonneman DJ, O’Connor RE, Phillippy AM, Rohrer GA, Rosen BD, Rund LA, Sargent CA, Schook LB, Schroeder SG, Schwartz AS, Skinner BM, Talbot R, Tseng E, Tuggle CK, Watson M, Smith TPL, Archibald AL (2019) An improved pig reference genome sequence to enable pig genetics and genomics research. bioRxiv. https://doi.org/10.1101/668921
Yan X, Hu Z, Feng Y, Hu X, Yuan J, Zhao SD, Zhang Y, Yang L, Shan W, He Q, Fan L, Kandalaft LE, Tanyi JL, Li C, Yuan C-X, Zhang D, Yuan H, Hua K, Lu Y, Katsaros D, Huang Q, Montone K, Fan Y, Coukos G, Boyd J, Sood AK, Rebbeck T, Mills GB, Dang CV, Zhang L (2015) Comprehensive genomic characterization of long non-coding RNAs across human cancers. Cancer Cell 28:529–540
Yang L, Güell M, Niu D, George H, Lesha E, Grishin D, Aach J, Shrock E, Xu W, Poci J, Cortazio R, Wilkinson RA, Fishman JA, Church G (2015) Genome-wide inactivation of porcine endogenous retroviruses (PERVs). Science 350(6264):1101–1104
Yang P, Wang Y, Macfarlan TS (2017) The role of KRAB-ZFPs in transposable element repression and mammalian evolution. Trends Genet 33:871–881. https://doi.org/10.1016/jtig201708006
Zhu Y, Yao S, Augustine MM, Xu H, Wang J, Sun J, Broadwater M, Ruff W, Luo L, Zhu G, Tamada K, Chen L (2016) Neuron-specific SALM5 limits inflammation in the CNS via its interaction with HVEM. Sci Adv 2:e1500637. https://doi.org/10.1126/sciadv1500637
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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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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DOI: https://doi.org/10.1007/s00438-020-01694-6