Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2019, Vol. 13 Issue (3) : 289-297    https://doi.org/10.1007/s11684-018-0667-3
REVIEW
Histone variants: critical determinants in tumour heterogeneity
Tao Wang1,2, Florent Chuffart1, Ekaterina Bourova-Flin1, Jin Wang2, Jianqing Mi2, Sophie Rousseaux1, Saadi Khochbin1()
1. CNRS UMR 5309, Inserm, U1209, University of Grenoble Alpes, Institute for Advanced Biosciences, 38706, Grenoble, France
2. State Key Laboratory for Medical Genomics and Department of Hematology, Shanghai Institute of Hematology, Collaborative Innovation Center of Systems Biomedicine, Pôle Sino-Français des Sciences du Vivant et Genomique, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
 Download: PDF(945 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

Malignant cell transformation could be considered as a series of cell reprogramming events driven by oncogenic transcription factors and upstream signalling pathways. Chromatin plasticity and dynamics are critical determinants in the control of cell reprograming. An increase in chromatin dynamics could therefore constitute an essential step in driving oncogenesis and in generating tumour cell heterogeneity, which is indispensable for the selection of aggressive properties, including the ability of cells to disseminate and acquire resistance to treatments. Histone supply and dosage, as well as histone variants, are the best-known regulators of chromatin dynamics. By facilitating cell reprogramming, histone under-dosage and histone variants should also be crucial in cell transformation and tumour metastasis. Here we summarize and discuss our knowledge of the role of histone supply and histone variants in chromatin dynamics and their ability to enhance oncogenic cell reprogramming and tumour heterogeneity.

Keywords cancer-testis      TH2B      TH2A      H1T      H1.0      H1F0      linker histones     
Corresponding Author(s): Saadi Khochbin   
Just Accepted Date: 28 August 2018   Online First Date: 09 October 2018    Issue Date: 05 June 2019
 Cite this article:   
Tao Wang,Florent Chuffart,Ekaterina Bourova-Flin, et al. Histone variants: critical determinants in tumour heterogeneity[J]. Front. Med., 2019, 13(3): 289-297.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0667-3
https://academic.hep.com.cn/fmd/EN/Y2019/V13/I3/289
Fig.1  Histone-based malignant transformation, tumour heterogeneity and selection of aggressive characters. Pro-oncogenic events could lead to aberrant activation of silenced histone variants-encoding genes or histone assembly defects or histone under-dosage, leading to increased chromatin dynamics and enhanced genome reprogramming by oncogenic factors. The resulting heterogeneity would create a window of opportunity for the selection of newly reprogrammed oncogenic cells capable of surviving and disseminating.
Fig.2  Aberrant activation of testis-oocyte specific TH2A/TH2B in various cancers. (A) Expression of TH2A and TH2B genes in normal human tissues samples from RNA-seq data, provided by the Genotype-Tissue Expression (GTEx) project [56]. (B) Expression of TH2A and TH2B genes in breast and lung cancer samples. Breast cancer RNA-seq data are provided by the TCGA-BRCA project [57]. Lung cancer RNA-seq data are provided by the NCBI GEO GSE81089 [58], TCGA-LUAD and TCGA-LUSC projects [57]. For all plots, the expression level of genes is represented as a distribution of log-transformed RPKM values, after addition of a pseudo count of 1 (log2 (1+RPKM)). Breast cancer: NT Breast= non tumoral breast; Breast K= breast cancer. Lung cancer: NT Lung= non tumoral lung; L. ADC= Lung adenocarcinoma; L. SQC= Lung squamous cell carcinoma; other LK= lung tumours of other histological subtypes.
Fig.3  Aberrant activation of testis-specific H1T in various cancers. Expression of H1T gene in normal (left panel) and tumour (right panels) samples from RNA-seq data, provided by the GTEx [56], TCGA-BRCA [57] and NCBI GEO GSE81089 [58] datasets. The expression level of genes is represented as a distribution of log-transformed RPKM values, after addition of a pseudo count of 1 (log2 (1+RPKM)). Breast cancer: NT Breast= non tumoral breast; Breast K= breast cancer. Lung cancer: NT Lung= non tumoral lung; L. ADC= Lung adenocarcinoma; L. SQC= Lung squamous cell carcinoma; other LK= lung tumours of other histological subtypes.
Fig.4  H1F0 gene expression is activated in different cancers. Expression of H1F0 gene in breast and lung tumour samples with corresponding Kaplan–Meyer survival curves. Breast cancer RNA-seq data are provided by the TCGA-BRCA project [57]. Lung cancer RNA-seq data are provided by the NCBI GEO GSE81089 [58], TCGA-LUAD and TCGA-LUSC projects [57]. For all plots, the expression level of genes is represented as a distribution of log-transformed RPKM values, after addition of a pseudo count of 1 (log2 (1+RPKM)). Breast cancer: NT Breast= non tumoral breast; Breast K= breast cancer. Lung cancer: NT Lung= non tumoral lung; L. ADC= Lung adenocarcinoma; L. SQC= Lung squamous cell carcinoma; L. LCNE= Lung large cell neuroendocrine tumours; L. BAS= Lung basaloid tumours; L. SCC= Lung small cell carcinoma; L. CARCI= Lung carcinoid tumours; other LK= lung tumours of other histological subtypes.
1 Y Assenov, D Brocks, C Gerhäuser. Intratumor heterogeneity in epigenetic patterns. Semin Cancer Biol 2018; 51: 12–21
https://doi.org/10.1016/j.semcancer.2018.01.010 pmid: 29366906
2 T Mazor, A Pankov, JS Song, JF Costello. Intratumoral heterogeneity of the epigenome. Cancer Cell 2016; 29(4): 440–451
https://doi.org/10.1016/j.ccell.2016.03.009 pmid: 27070699
3 D Hanahan, RA Weinberg. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646–674
https://doi.org/10.1016/j.cell.2011.02.013 pmid: 21376230
4 K Takahashi, S Yamanaka. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126(4): 663–676
https://doi.org/10.1016/j.cell.2006.07.024 pmid: 16904174
5 S Ecker, V Pancaldi, A Valencia, S Beck, DS Paul. Epigenetic and transcriptional variability shape phenotypic plasticity. BioEssays 2018; 40(2): 1700148
https://doi.org/10.1002/bies.201700148 pmid: 29251357
6 A Puisieux, RM Pommier, AP Morel, F Lavial. Cellular pliancy and the multistep process of tumorigenesis. Cancer Cell 2018; 33(2): 164–172
https://doi.org/10.1016/j.ccell.2018.01.007 pmid: 29438693
7 A Decottignies, F d’Adda di Fagagna. Epigenetic alterations associated with cellular senescence: a barrier against tumorigenesis or a red carpet for cancer? Semin Cancer Biol 2011; 21(6): 360–366
https://doi.org/10.1016/j.semcancer.2011.09.003 pmid: 21946622
8 DD De Carvalho, JS You, PA Jones. DNA methylation and cellular reprogramming. Trends Cell Biol 2010; 20(10): 609–617
https://doi.org/10.1016/j.tcb.2010.08.003 pmid: 20810283
9 JS Becker, D Nicetto, KS Zaret. H3K9me3-dependent heterochromatin: barrier to cell fate changes. Trends Genet 2016; 32(1): 29–41
https://doi.org/10.1016/j.tig.2015.11.001 pmid: 26675384
10 A Burton, ME Torres-Padilla. Chromatin dynamics in the regulation of cell fate allocation during early embryogenesis. Nat Rev Mol Cell Biol 2014; 15(11): 723–734
https://doi.org/10.1038/nrm3885 pmid: 25303116
11 E Apostolou, K Hochedlinger. Chromatin dynamics during cellular reprogramming. Nature 2013; 502(7472): 462–471
https://doi.org/10.1038/nature12749 pmid: 24153299
12 S Cheloufi, K Hochedlinger. Emerging roles of the histone chaperone CAF-1 in cellular plasticity. Curr Opin Genet Dev 2017; 46: 83–94
https://doi.org/10.1016/j.gde.2017.06.004 pmid: 28692904
13 MH Hauer, SM Gasser. Chromatin and nucleosome dynamics in DNA damage and repair. Genes Dev 2017; 31(22): 2204–2221
https://doi.org/10.1101/gad.307702.117 pmid: 29284710
14 N Hoghoughi, S Barral, A Vargas, S Rousseaux, S Khochbin. Histone variants: essential actors in male genome programming. J Biochem 2018; 163(2): 97–103
https://doi.org/10.1093/jb/mvx079 pmid: 29165574
15 X Gaume, ME Torres-Padilla. Regulation of reprogramming and cellular plasticity through histone exchange and histone variant incorporation. Cold Spring Harb Symp Quant Biol 2015; 80: 165–175
https://doi.org/10.1101/sqb.2015.80.027458 pmid: 26582788
16 P Yang, W Wu, TS Macfarlan. Maternal histone variants and their chaperones promote paternal genome activation and boost somatic cell reprogramming. BioEssays 2015; 37(1): 52–59
https://doi.org/10.1002/bies.201400072 pmid: 25328107
17 ZA Gurard-Levin, JP Quivy, G Almouzni. Histone chaperones: assisting histone traffic and nucleosome dynamics. Annu Rev Biochem 2014; 83(1): 487–517
https://doi.org/10.1146/annurev-biochem-060713-035536 pmid: 24905786
18 S Cheloufi, U Elling, B Hopfgartner, YL Jung, J Murn, M Ninova, M Hubmann, AI Badeaux, C Euong Ang, D Tenen, DJ Wesche, N Abazova, M Hogue, N Tasdemir, J Brumbaugh, P Rathert, J Jude, F Ferrari, A Blanco, M Fellner, D Wenzel, M Zinner, SE Vidal, O Bell, M Stadtfeld, HY Chang, G Almouzni, SW Lowe, J Rinn, M Wernig, A Aravin, Y Shi, PJ Park, JM Penninger, J Zuber, K Hochedlinger. The histone chaperone CAF-1 safeguards somatic cell identity. Nature 2015; 528(7581): 218–224
https://doi.org/10.1038/nature15749 pmid: 26659182
19 T Ishiuchi, R Enriquez-Gasca, E Mizutani, A Bošković, C Ziegler-Birling, D Rodriguez-Terrones, T Wakayama, JM Vaquerizas, ME Torres-Padilla. Early embryonic-like cells are induced by downregulating replication-dependent chromatin assembly. Nat Struct Mol Biol 2015; 22(9): 662–671
https://doi.org/10.1038/nsmb.3066 pmid: 26237512
20 C Rivera-Casas, R Gonzalez-Romero, MS Cheema, J Ausió, JM Eirín-López. The characterization of macroH2A beyond vertebrates supports an ancestral origin and conserved role for histone variants in chromatin. Epigenetics 2016; 11(6): 415–425
https://doi.org/10.1080/15592294.2016.1172161 pmid: 27082816
21 TA Soboleva, M Nekrasov, A Pahwa, R Williams, GA Huttley, DJ Tremethick. A unique H2A histone variant occupies the transcriptional start site of active genes. Nat Struct Mol Biol 2011; 19(1): 25–30
https://doi.org/10.1038/nsmb.2161 pmid: 22139013
22 S Barral, Y Morozumi, H Tanaka, E Montellier, J Govin, M de Dieuleveult, G Charbonnier, Y Couté, D Puthier, T Buchou, F Boussouar, T Urahama, F Fenaille, S Curtet, P Héry, N Fernandez-Nunez, H Shiota, M Gérard, S Rousseaux, H Kurumizaka, S Khochbin. Histone variant H2A.L.2 guides transition protein-dependent protamine assembly in male germ cells. Mol Cell 2017; 66(1): 89–101.e8
https://doi.org/10.1016/j.molcel.2017.02.025 pmid: 28366643
23 V Pasque, A Gillich, N Garrett, JB Gurdon. Histone variant macroH2A confers resistance to nuclear reprogramming. EMBO J 2011; 30(12): 2373–2387
https://doi.org/10.1038/emboj.2011.144 pmid: 21552206
24 T Shinagawa, T Takagi, D Tsukamoto, C Tomaru, LM Huynh, P Sivaraman, T Kumarevel, K Inoue, R Nakato, Y Katou, T Sado, S Takahashi, A Ogura, K Shirahige, S Ishii. Histone variants enriched in oocytes enhance reprogramming to induced pluripotent stem cells. Cell Stem Cell 2014; 14(2): 217–227
https://doi.org/10.1016/j.stem.2013.12.015 pmid: 24506885
25 D Quénet. Histone variants and disease. Int Rev Cell Mol Biol 2018; 335: 1–39
https://doi.org/10.1016/bs.ircmb.2017.07.006 pmid: 29305010
26 S Rousseaux, A Debernardi, B Jacquiau, AL Vitte, A Vesin, H Nagy-Mignotte, D Moro-Sibilot, PY Brichon, S Lantuejoul, P Hainaut, J Laffaire, A de Reyniès, DG Beer, JF Timsit, C Brambilla, E Brambilla, S Khochbin. Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers. Sci Transl Med 2013; 5(186): 186ra66
https://doi.org/10.1126/scitranslmed.3005723 pmid: 23698379
27 J Govin, C Caron, S Rousseaux, S Khochbin. Testis-specific histone H3 expression in somatic cells. Trends Biochem Sci 2005; 30(7): 357–359
https://doi.org/10.1016/j.tibs.2005.05.001 pmid: 15922600
28 F Mohammad, K Helin. Oncohistones: drivers of pediatric cancers. Genes Dev 2017; 31(23-24): 2313–2324
https://doi.org/10.1101/gad.309013.117 pmid: 29352018
29 J Gaucher, N Reynoird, E Montellier, F Boussouar, S Rousseaux, S Khochbin. From meiosis to postmeiotic events: the secrets of histone disappearance. FEBS J 2010; 277(3): 599–604
https://doi.org/10.1111/j.1742-4658.2009.07504.x pmid: 20015078
30 J Ueda, A Harada, T Urahama, S Machida, K Maehara, M Hada, Y Makino, J Nogami, N Horikoshi, A Osakabe, H Taguchi, H Tanaka, H Tachiwana, T Yao, M Yamada, T Iwamoto, A Isotani, M Ikawa, T Tachibana, Y Okada, H Kimura, Y Ohkawa, H Kurumizaka, K Yamagata. Testis-specific histone variant H3t gene is essential for entry into spermatogenesis. Cell Reports 2017; 18(3): 593–600
https://doi.org/10.1016/j.celrep.2016.12.065 pmid: 28099840
31 H Tachiwana, W Kagawa, A Osakabe, K Kawaguchi, T Shiga, Y Hayashi-Takanaka, H Kimura, H Kurumizaka. Structural basis of instability of the nucleosome containing a testis-specific histone variant, human H3T. Proc Natl Acad Sci USA 2010; 107(23): 10454–10459
https://doi.org/10.1073/pnas.1003064107 pmid: 20498094
32 J Zhou, JY Fan, D Rangasamy, DJ Tremethick. The nucleosome surface regulates chromatin compaction and couples it with transcriptional repression. Nat Struct Mol Biol 2007; 14(11): 1070–1076
https://doi.org/10.1038/nsmb1323 pmid: 17965724
33 E Montellier, F Boussouar, S Rousseaux, K Zhang, T Buchou, F Fenaille, H Shiota, A Debernardi, P Héry, S Curtet, M Jamshidikia, S Barral, H Holota, A Bergon, F Lopez, P Guardiola, K Pernet, J Imbert, C Petosa, M Tan, Y Zhao, M Gérard, S Khochbin. Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B. Genes Dev 2013; 27(15): 1680–1692
https://doi.org/10.1101/gad.220095.113 pmid: 23884607
34 T Shinagawa, LM Huynh, T Takagi, D Tsukamoto, C Tomaru, HG Kwak, N Dohmae, J Noguchi, S Ishii. Disruption of Th2a and Th2b genes causes defects in spermatogenesis. Development 2015; 142(7): 1287–1292
https://doi.org/10.1242/dev.121830 pmid: 25742800
35 D Iuso, M Czernik, P Toschi, A Fidanza, F Zacchini, R Feil, S Curtet, T Buchou, H Shiota, S Khochbin, GE Ptak, P Loi. Exogenous expression of human protamine 1 (hPrm1) remodels fibroblast nuclei into spermatid-like structures. Cell Reports 2015; 13(9): 1765–1771
https://doi.org/10.1016/j.celrep.2015.10.066 pmid: 26628361
36 JV Chodaparambil, AJ Barbera, X Lu, KM Kaye, JC Hansen, K Luger. A charged and contoured surface on the nucleosome regulates chromatin compaction. Nat Struct Mol Biol 2007; 14(11): 1105–1107
https://doi.org/10.1038/nsmb1334 pmid: 17965723
37 K Luger, AW Mäder, RK Richmond, DF Sargent, TJ Richmond. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 1997; 389(6648): 251–260
https://doi.org/10.1038/38444 pmid: 9305837
38 A Molaro, JM Young, HS Malik. Evolutionary origins and diversification of testis-specific short histone H2A variants in mammals. Genome Res 2018; 28(4): 460–473
https://doi.org/10.1101/gr.229799.117 pmid: 29549088
39 Y Bao, K Konesky, YJ Park, S Rosu, PN Dyer, D Rangasamy, DJ Tremethick, PJ Laybourn, K Luger. Nucleosomes containing the histone variant H2A.Bbd organize only 118 base pairs of DNA. EMBO J 2004; 23(16): 3314–3324
https://doi.org/10.1038/sj.emboj.7600316 pmid: 15257289
40 SH Syed, M Boulard, MS Shukla, T Gautier, A Travers, J Bednar, C Faivre-Moskalenko, S Dimitrov, D Angelov. The incorporation of the novel histone variant H2AL2 confers unusual structural and functional properties of the nucleosome. Nucleic Acids Res 2009; 37(14): 4684–4695
https://doi.org/10.1093/nar/gkp473 pmid: 19506029
41 C Winkler, DS Steingrube, W Altermann, G Schlaf, D Max, S Kewitz, A Emmer, M Kornhuber, U Banning-Eichenseer, MS Staege. Hodgkin’s lymphoma RNA-transfected dendritic cells induce cancer/testis antigen-specific immune responses. Cancer Immunol Immunother 2012; 61(10): 1769–1779
https://doi.org/10.1007/s00262-012-1239-z pmid: 22419371
42 V Sansoni, CS Casas-Delucchi, M Rajan, A Schmidt, C Bönisch, AW Thomae, MS Staege, SB Hake, MC Cardoso, A Imhof. The histone variant H2A.Bbd is enriched at sites of DNA synthesis. Nucleic Acids Res 2014; 42(10): 6405–6420
https://doi.org/10.1093/nar/gku303 pmid: 24753410
43 S Khochbin. Histone H1 diversity: bridging regulatory signals to linker histone function. Gene 2001; 271(1): 1–12
https://doi.org/10.1016/S0378-1119(01)00495-4 pmid: 11410360
44 M Peretti, S Khochbin. The evolution of the differentiation-specific histone H1 gene basal promoter. J Mol Evol 1997; 44(2): 128–134
https://doi.org/10.1007/PL00006129 pmid: 9069173
45 D Rousseau, S Khochbin, C Gorka, JJ Lawrence. Regulation of histone H1(0) accumulation during induced differentiation of murine erythroleukemia cells. J Mol Biol 1991; 217(1): 85–92
https://doi.org/10.1016/0022-2836(91)90613-B pmid: 1988682
46 D Rousseau, S Khochbin, C Gorka, JJ Lawrence. Induction of H1(0)-gene expression in B16 murine melanoma cells. Eur J Biochem 1992; 208(3): 775–779
https://doi.org/10.1111/j.1432-1033.1992.tb17247.x pmid: 1396682
47 S Khochbin, AP Wolffe. Developmental regulation and butyrate-inducible transcription of the Xenopus histone H1(0) promoter. Gene 1993; 128(2): 173–180
https://doi.org/10.1016/0378-1119(93)90560-P pmid: 8514185
48 D Seigneurin, D Grunwald, JJ Lawrence, S Khochbin. Developmentally regulated chromatin acetylation and histone H1(0) accumulation. Int J Dev Biol 1995; 39(4): 597–603
pmid: 8619958
49 D Grunwald, JJ Lawrence, S Khochbin. Accumulation of histone H1(0) during early Xenopus laevis development. Exp Cell Res 1995; 218(2): 586–595
https://doi.org/10.1006/excr.1995.1196 pmid: 7796895
50 A Izzo, C Ziegler-Birling, PWS Hill, L Brondani, P Hajkova, ME Torres-Padilla, R Schneider. Dynamic changes in H1 subtype composition during epigenetic reprogramming. J Cell Biol 2017; jcb.201611012
https://doi.org/10.1083/jcb.201611012 pmid: 28794128
51 CM Torres, A Biran, MJ Burney, H Patel, T Henser-Brownhill, AS Cohen, Y Li, R Ben-Hamo, E Nye, B Spencer-Dene, P Chakravarty, S Efroni, N Matthews, T Misteli, E Meshorer, P Scaffidi. The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity. Science 2016; 353(6307): aaf1644
https://doi.org/10.1126/science.aaf1644 pmid: 27708074
52 C Gorka, JJ Lawrence, S Khochbin. Variation of H1(0) content throughout the cell cycle in regenerating rat liver. Exp Cell Res 1995; 217(2): 528–533
https://doi.org/10.1006/excr.1995.1118 pmid: 7698253
53 S Khochbin, AP Wolffe. Developmentally regulated expression of linker-histone variants in vertebrates. Eur J Biochem 1994; 225(2): 501–510
https://doi.org/10.1111/j.1432-1033.1994.00501.x pmid: 7957165
54 D Grunwald, S Khochbin, JJ Lawrence. Cell cycle-related accumulation of H1(0) mRNA: induction in murine erythroleukemia cells. Exp Cell Res 1991; 194(2): 174–179
https://doi.org/10.1016/0014-4827(91)90350-4 pmid: 2026174
55 MP Brocard, S Triebe, M Peretti, D Doenecke, S Khochbin. Characterization of the two H1(zero)-encoding genes from Xenopus laevis. Gene 1997; 189(1): 127–134
https://doi.org/10.1016/S0378-1119(96)00845-1 pmid: 9161423
56 J Lonsdale, J Thomas, M Salvatore, R Phillips, E Lo, S Shad, R Hasz, G Walters, F Garcia, N Young, B Foster, M Moser, E Karasik, B Gillard, K Ramsey, S Sullivan, J Bridge, H Magazine, J Syron, J Fleming, L Siminoff, H Traino, M Mosavel, L Barker, S Jewell, D Rohrer, D Maxim, D Filkins, P Harbach, E Cortadillo, B Berghuis, L Turner, E Hudson, K Feenstra, L Sobin, J Robb, P Branton, G Korzeniewski, C Shive, D Tabor, L Qi, K Groch, S Nampally, S Buia, A Zimmerman, A Smith, R Burges, K Robinson, K Valentino, D Bradbury, M Cosentino, N Diaz-Mayoral, M Kennedy, T Engel, P Williams, K Erickson, K Ardlie, W Winckler, G Getz, D DeLuca, D MacArthur, M Kellis, A Thomson, T Young, E Gelfand, M Donovan, Y Meng, G Grant, D Mash, Y Marcus, M Basile, J Liu, J Zhu, Z Tu, NJ Cox, DL Nicolae, ER Gamazon, HK Im, A Konkashbaev, J Pritchard, M Stevens, T Flutre, X Wen, ET Dermitzakis, T Lappalainen, R Guigo, J Monlong, M Sammeth, D Koller, A Battle, S Mostafavi, M McCarthy, M Rivas, J Maller, I Rusyn, A Nobel, F Wright, A Shabalin, M Feolo, N Sharopova, A Sturcke, J Paschal, JM Anderson, EL Wilder, LK Derr, ED Green, JP Struewing, G Temple, S Volpi, JT Boyer, EJ Thomson, MS Guyer, C Ng, A Abdallah, D Colantuoni, TR Insel, SE Koester, AR Little, PK Bender, T Lehner, Y Yao, CC Compton, JB Vaught, S Sawyer, NC Lockhart, J Demchok, HF Moore; GTEx Consortium. The Genotype-Tissue Expression (GTEx) project. Nat Genet 2013; 45(6): 580–585
https://doi.org/10.1038/ng.2653 pmid: 23715323
57 L Peng, XW Bian, DK Li, C Xu, GM Wang, QY Xia, Q Xiong. Large-scale RNA-seq transcriptome analysis of 4043 cancers and 548 normal tissue controls across 12 TCGA cancer types. Sci Rep 2015; 5(1): 13413
https://doi.org/10.1038/srep13413 pmid: 26292924
58 D Djureinovic, BM Hallström, M Horie, JSM Mattsson, L La Fleur, L Fagerberg, H Brunnström, C Lindskog, K Madjar, J Rahnenführer, S Ekman, E Ståhle, H Koyi, E Brandén, K Edlund, JG Hengstler, M Lambe, A Saito, J Botling, F Pontén, M Uhlén, P Micke. Profiling cancer testis antigens in non-small-cell lung cancer. JCI Insight 2016; 1(10): e86837
https://doi.org/10.1172/jci.insight.86837 pmid: 27699219
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed