Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers

Activation of normally silent tissue-specific genes and the resulting cell "identity crisis" are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricte...

Full description

Saved in:

Bibliographic Details
Published in:	Science translational medicine Vol. 5; no. 186; p. 186ra66
Main Authors:	Rousseaux, Sophie, Debernardi, Alexandra, Jacquiau, Baptiste, Vitte, Anne-Laure, Vesin, Aurélien, Nagy-Mignotte, Hélène, Moro-Sibilot, Denis, Brichon, Pierre-Yves, Lantuejoul, Sylvie, Hainaut, Pierre, Laffaire, Julien, de Reyniès, Aurélien, Beer, David G, Timsit, Jean-François, Brambilla, Christian, Brambilla, Elisabeth, Khochbin, Saadi
Format:	Journal Article
Language:	English
Published:	United States 22.05.2013
Subjects:	Animals Cell Line, Tumor DNA Methylation - genetics Epigenesis, Genetic Female Gene Expression Regulation, Neoplastic Germ Cells - metabolism Humans Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - pathology Neoplasm Invasiveness Neoplasm Metastasis - genetics Neoplasm Staging Organ Specificity Placenta - metabolism Pregnancy Prognosis Promoter Regions, Genetic - genetics Reproducibility of Results Transcriptome
ISSN:	1946-6242, 1946-6242
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Abstract	Activation of normally silent tissue-specific genes and the resulting cell "identity crisis" are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. This approach led to the demonstration that large-scale "off-context" gene activations systematically occur in a variety of cancer types. In our series of 293 lung tumors, we identified an ectopic gene expression signature associated with a subset of highly aggressive tumors, which predicted poor prognosis independently of the TNM (tumor size, node positivity, and metastasis) stage or histological subtype. The ability to isolate these tumors allowed us to reveal their common molecular features characterized by the acquisition of embryonic stem cell/germ cell gene expression profiles and the down-regulation of immune response genes. The methodical recognition of ectopic gene activations in cancer cells could serve as a basis for gene signature-guided tumor stratification, as well as for the discovery of oncogenic mechanisms, and expand the understanding of the biology of very aggressive tumors.
AbstractList	Activation of normally silent tissue-specific genes and the resulting cell "identity crisis" are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. This approach led to the demonstration that large-scale "off-context" gene activations systematically occur in a variety of cancer types. In our series of 293 lung tumors, we identified an ectopic gene expression signature associated with a subset of highly aggressive tumors, which predicted poor prognosis independently of the TNM (tumor size, node positivity, and metastasis) stage or histological subtype. The ability to isolate these tumors allowed us to reveal their common molecular features characterized by the acquisition of embryonic stem cell/germ cell gene expression profiles and the down-regulation of immune response genes. The methodical recognition of ectopic gene activations in cancer cells could serve as a basis for gene signature-guided tumor stratification, as well as for the discovery of oncogenic mechanisms, and expand the understanding of the biology of very aggressive tumors. Activation of normally silent tissue-specific genes and the resulting cell "identity crisis" are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. This approach led to the demonstration that large-scale "off-context" gene activations systematically occur in a variety of cancer types. In our series of 293 lung tumors, we identified an ectopic gene expression signature associated with a subset of highly aggressive tumors, which predicted poor prognosis independently of the TNM (tumor size, node positivity, and metastasis) stage or histological subtype. The ability to isolate these tumors allowed us to reveal their common molecular features characterized by the acquisition of embryonic stem cell/germ cell gene expression profiles and the down-regulation of immune response genes. The methodical recognition of ectopic gene activations in cancer cells could serve as a basis for gene signature-guided tumor stratification, as well as for the discovery of oncogenic mechanisms, and expand the understanding of the biology of very aggressive tumors.Activation of normally silent tissue-specific genes and the resulting cell "identity crisis" are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. This approach led to the demonstration that large-scale "off-context" gene activations systematically occur in a variety of cancer types. In our series of 293 lung tumors, we identified an ectopic gene expression signature associated with a subset of highly aggressive tumors, which predicted poor prognosis independently of the TNM (tumor size, node positivity, and metastasis) stage or histological subtype. The ability to isolate these tumors allowed us to reveal their common molecular features characterized by the acquisition of embryonic stem cell/germ cell gene expression profiles and the down-regulation of immune response genes. The methodical recognition of ectopic gene activations in cancer cells could serve as a basis for gene signature-guided tumor stratification, as well as for the discovery of oncogenic mechanisms, and expand the understanding of the biology of very aggressive tumors.
Author	Brichon, Pierre-Yves Beer, David G Rousseaux, Sophie Nagy-Mignotte, Hélène Brambilla, Christian Moro-Sibilot, Denis Hainaut, Pierre Laffaire, Julien de Reyniès, Aurélien Lantuejoul, Sylvie Timsit, Jean-François Debernardi, Alexandra Jacquiau, Baptiste Vitte, Anne-Laure Vesin, Aurélien Brambilla, Elisabeth Khochbin, Saadi
Author_xml	– sequence: 1 givenname: Sophie surname: Rousseaux fullname: Rousseaux, Sophie email: sophie.rousseaux@ujf-grenoble.fr organization: INSERM, U823, Université Joseph Fourier, Grenoble 1, Institut Albert Bonniot, Grenoble F-38700, France. sophie.rousseaux@ujf-grenoble.fr – sequence: 2 givenname: Alexandra surname: Debernardi fullname: Debernardi, Alexandra – sequence: 3 givenname: Baptiste surname: Jacquiau fullname: Jacquiau, Baptiste – sequence: 4 givenname: Anne-Laure surname: Vitte fullname: Vitte, Anne-Laure – sequence: 5 givenname: Aurélien surname: Vesin fullname: Vesin, Aurélien – sequence: 6 givenname: Hélène surname: Nagy-Mignotte fullname: Nagy-Mignotte, Hélène – sequence: 7 givenname: Denis surname: Moro-Sibilot fullname: Moro-Sibilot, Denis – sequence: 8 givenname: Pierre-Yves surname: Brichon fullname: Brichon, Pierre-Yves – sequence: 9 givenname: Sylvie surname: Lantuejoul fullname: Lantuejoul, Sylvie – sequence: 10 givenname: Pierre surname: Hainaut fullname: Hainaut, Pierre – sequence: 11 givenname: Julien surname: Laffaire fullname: Laffaire, Julien – sequence: 12 givenname: Aurélien surname: de Reyniès fullname: de Reyniès, Aurélien – sequence: 13 givenname: David G surname: Beer fullname: Beer, David G – sequence: 14 givenname: Jean-François surname: Timsit fullname: Timsit, Jean-François – sequence: 15 givenname: Christian surname: Brambilla fullname: Brambilla, Christian – sequence: 16 givenname: Elisabeth surname: Brambilla fullname: Brambilla, Elisabeth – sequence: 17 givenname: Saadi surname: Khochbin fullname: Khochbin, Saadi
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23698379$$D View this record in MEDLINE/PubMed
BookMark	eNpNUMtKxDAUDTLiPPQPRLJ007FN0rRdyjA-YMCNrkt6c1MiaVqbzIB_b8ARhAvnweFyOGuy8KNHQm6LfFsUTD4EsHFWPrgB9ZbneVkxfkFWRSNkJplgi398SdYhfOa5rHkpr8iScdnUvGpWxOwhjpMFqiDak4p29HQ0tMd5cNYjVV7TySlAH5VLtsdArU7KGpuo6vsZQ7AnpANGFdLZkE1zqkrd0fcUlAecwzW5NMoFvDnjhnw87d93L9nh7fl193jIQEgWsxoBjJCdZEwDCKhVZbRsOixMhbUQpja6aEynG8GlaSoQRjCopDGaCVlytiH3v39Tha8jhtgONgA6pzyOx9AWvCxFVUlWpujdOXrs0oTtNNtBzd_t3zbsBzy0bg0
CitedBy_id	crossref_primary_10_1111_cbdd_13672 crossref_primary_10_1038_s41598_020_78126_3 crossref_primary_10_1126_sciadv_ads4227 crossref_primary_10_1016_j_semcancer_2017_09_005 crossref_primary_10_1007_s12026_022_09335_3 crossref_primary_10_1016_j_athoracsur_2019_08_050 crossref_primary_10_3390_cancers14102384 crossref_primary_10_1016_j_ebiom_2020_102959 crossref_primary_10_3390_jpm10040263 crossref_primary_10_1111_jcmm_18516 crossref_primary_10_1158_1078_0432_CCR_14_0459 crossref_primary_10_3389_fimmu_2024_1481753 crossref_primary_10_1111_bjd_20760 crossref_primary_10_1155_2020_8832739 crossref_primary_10_1186_s40164_024_00546_y crossref_primary_10_3892_or_2022_8342 crossref_primary_10_1093_bib_bbv064 crossref_primary_10_3892_mmr_2023_13043 crossref_primary_10_1016_j_imbio_2022_152239 crossref_primary_10_3389_fimmu_2025_1634830 crossref_primary_10_1002_emmm_201202034 crossref_primary_10_1038_s41422_019_0181_4 crossref_primary_10_1186_s12885_023_10622_x crossref_primary_10_3389_fmed_2022_855387 crossref_primary_10_1007_s12672_024_00939_9 crossref_primary_10_1002_jcp_31109 crossref_primary_10_1016_j_canlet_2017_04_021 crossref_primary_10_1016_j_lungcan_2014_05_011 crossref_primary_10_1038_s41416_021_01491_x crossref_primary_10_1016_j_intimp_2023_111286 crossref_primary_10_1007_s10529_020_02951_9 crossref_primary_10_3390_nano9020295 crossref_primary_10_1007_s00018_020_03490_2 crossref_primary_10_3389_fbioe_2020_00582 crossref_primary_10_1007_s00432_023_05390_x crossref_primary_10_1159_000354284 crossref_primary_10_1007_s00262_021_03066_4 crossref_primary_10_1038_s41598_023_47659_8 crossref_primary_10_1016_j_yexcr_2021_112653 crossref_primary_10_1038_s41598_024_62569_z crossref_primary_10_3389_fonc_2021_733533 crossref_primary_10_3389_fcell_2021_719011 crossref_primary_10_7717_peerj_16306 crossref_primary_10_1038_s41467_022_29230_7 crossref_primary_10_1098_rsob_180081 crossref_primary_10_1007_s13277_015_3572_2 crossref_primary_10_1186_s12859_019_2775_8 crossref_primary_10_1002_tox_24230 crossref_primary_10_3389_fimmu_2022_1058493 crossref_primary_10_3892_or_2016_4817 crossref_primary_10_1016_j_jare_2024_11_001 crossref_primary_10_1038_s41467_024_45585_5 crossref_primary_10_1186_s13045_016_0339_1 crossref_primary_10_3389_fonc_2017_00304 crossref_primary_10_1016_j_bulcan_2019_08_003 crossref_primary_10_1186_s40364_016_0058_3 crossref_primary_10_1007_s13577_024_01109_3 crossref_primary_10_3389_fgene_2023_1156322 crossref_primary_10_3389_fimmu_2024_1347770 crossref_primary_10_3389_fphar_2022_1081244 crossref_primary_10_1007_s00438_023_02033_1 crossref_primary_10_1002_biof_2128 crossref_primary_10_1038_s41467_018_04572_3 crossref_primary_10_1016_j_ebiom_2014_10_012 crossref_primary_10_1002_path_4549 crossref_primary_10_3389_fonc_2021_759497 crossref_primary_10_1111_jcmm_18284 crossref_primary_10_2147_IJGM_S365695 crossref_primary_10_1074_jbc_M116_762757 crossref_primary_10_3389_fgene_2022_921837 crossref_primary_10_1097_MD_0000000000014714 crossref_primary_10_1186_s10020_025_01267_6 crossref_primary_10_1186_s12874_022_01530_y crossref_primary_10_1155_2020_3416807 crossref_primary_10_1016_j_mod_2014_12_003 crossref_primary_10_1038_s41467_021_24537_3 crossref_primary_10_3892_ijo_2019_4899 crossref_primary_10_7717_peerj_19121 crossref_primary_10_3892_ol_2017_6467 crossref_primary_10_1038_s41467_024_47314_4 crossref_primary_10_1007_s11684_018_0667_3 crossref_primary_10_1007_s12672_025_02560_w crossref_primary_10_1038_s42003_021_01842_7 crossref_primary_10_1136_jitc_2024_010008 crossref_primary_10_1016_j_intimp_2021_107564 crossref_primary_10_1038_srep11766 crossref_primary_10_1155_2022_1560199 crossref_primary_10_3389_fphar_2022_934722 crossref_primary_10_1016_j_devcel_2019_04_015 crossref_primary_10_3389_fcell_2021_743724 crossref_primary_10_1158_1078_0432_CCR_21_0136 crossref_primary_10_1073_pnas_2412854122 crossref_primary_10_1186_s12943_017_0653_4 crossref_primary_10_3389_fgene_2023_1083593 crossref_primary_10_1186_s12920_022_01340_7 crossref_primary_10_3389_fimmu_2021_698236 crossref_primary_10_3390_cancers13205135 crossref_primary_10_3389_fimmu_2022_1048503 crossref_primary_10_1111_cpr_13703 crossref_primary_10_3390_genes12111814 crossref_primary_10_1016_j_yexmp_2024_104882 crossref_primary_10_1002_ijc_28577 crossref_primary_10_1158_0008_5472_CAN_16_0356 crossref_primary_10_1093_bib_bbab212 crossref_primary_10_1155_2020_8458190 crossref_primary_10_1007_s10238_024_01439_4 crossref_primary_10_1016_j_heliyon_2023_e23502 crossref_primary_10_1038_s41598_025_90532_z crossref_primary_10_31083_j_fbl2906204 crossref_primary_10_1177_2045893217746054 crossref_primary_10_1016_j_jtho_2016_02_009 crossref_primary_10_1111_jcmm_70731 crossref_primary_10_1007_s00180_023_01346_4 crossref_primary_10_1016_j_prp_2020_152836 crossref_primary_10_4161_cc_25545 crossref_primary_10_1007_s00408_022_00537_y crossref_primary_10_1111_cas_13078 crossref_primary_10_3389_fgene_2020_00420 crossref_primary_10_3389_fmolb_2021_653805 crossref_primary_10_3390_onco2040017 crossref_primary_10_1002_ijc_33242 crossref_primary_10_1002_cam4_190 crossref_primary_10_1126_sciimmunol_abh2383 crossref_primary_10_1111_his_14918 crossref_primary_10_1016_j_ebiom_2022_104268 crossref_primary_10_1016_j_lungcan_2014_03_021 crossref_primary_10_6061_clinics_2021_e3222 crossref_primary_10_1002_cam4_5109 crossref_primary_10_3892_ol_2024_14509 crossref_primary_10_1016_j_ebiom_2018_02_017 crossref_primary_10_1093_nar_gkv229 crossref_primary_10_1038_s41598_024_60132_4 crossref_primary_10_1073_pnas_1904498116 crossref_primary_10_1093_nar_gkw797 crossref_primary_10_1038_s41416_021_01572_x crossref_primary_10_1016_j_jtho_2016_02_002 crossref_primary_10_1371_journal_pgen_1005442 crossref_primary_10_1007_s10585_018_9912_z crossref_primary_10_1007_s12672_025_03484_1 crossref_primary_10_1111_cas_15481 crossref_primary_10_1136_jitc_2024_010787 crossref_primary_10_3389_fonc_2019_01515 crossref_primary_10_1038_s41389_024_00513_6 crossref_primary_10_3389_fimmu_2023_1276074 crossref_primary_10_1016_j_ccell_2019_10_008 crossref_primary_10_1016_j_ebiom_2021_103301 crossref_primary_10_1007_s13402_023_00883_w crossref_primary_10_1186_s12935_021_02358_0 crossref_primary_10_1097_MD_0000000000040060 crossref_primary_10_2217_pme_2020_0112 crossref_primary_10_1002_cam4_4386 crossref_primary_10_1016_j_omtn_2023_08_005 crossref_primary_10_3892_ol_2018_9620 crossref_primary_10_7554_eLife_98903 crossref_primary_10_3389_fonc_2023_1274439 crossref_primary_10_3389_fcell_2021_780461 crossref_primary_10_1073_pnas_1508057112 crossref_primary_10_3892_mmr_2019_10061 crossref_primary_10_1093_carcin_bgy016 crossref_primary_10_1007_s12672_025_01981_x crossref_primary_10_1002_emmm_201303018 crossref_primary_10_1016_j_jtho_2016_08_141 crossref_primary_10_1038_s41388_024_03002_7 crossref_primary_10_1002_2211_5463_13860 crossref_primary_10_1002_tox_24284 crossref_primary_10_1007_s13277_015_3938_5 crossref_primary_10_7717_peerj_11687 crossref_primary_10_1002_iub_2768 crossref_primary_10_1016_j_prp_2022_154018 crossref_primary_10_3389_fonc_2021_629333 crossref_primary_10_3389_fimmu_2023_1274223 crossref_primary_10_7717_peerj_17545 crossref_primary_10_1111_jcmm_18520 crossref_primary_10_1089_ars_2013_5581 crossref_primary_10_1038_modpathol_2017_14 crossref_primary_10_3390_ijms24032382 crossref_primary_10_1016_j_csbj_2023_11_018 crossref_primary_10_3390_ijms25168869 crossref_primary_10_1111_1759_7714_70140 crossref_primary_10_1038_s41598_021_88209_4 crossref_primary_10_1200_JCO_2015_63_0970 crossref_primary_10_1111_jcmm_18408 crossref_primary_10_1158_2326_6066_CIR_16_0392 crossref_primary_10_1186_s13046_019_1272_2 crossref_primary_10_1016_j_ygeno_2022_110425 crossref_primary_10_1186_s12931_024_02870_7 crossref_primary_10_3389_fonc_2022_854999 crossref_primary_10_3389_fcell_2023_1224069 crossref_primary_10_1038_s42003_021_02323_7 crossref_primary_10_1186_s13046_019_1286_9 crossref_primary_10_3389_fcell_2021_682619 crossref_primary_10_1016_j_lungcan_2024_107791 crossref_primary_10_1080_2162402X_2020_1824641 crossref_primary_10_1080_2162402X_2018_1494677 crossref_primary_10_1186_s12943_022_01705_7 crossref_primary_10_1186_s12967_025_06489_0 crossref_primary_10_1186_s12951_025_03404_z crossref_primary_10_3892_ol_2018_9044 crossref_primary_10_3892_or_2016_5289 crossref_primary_10_1158_0008_5472_CAN_17_1535 crossref_primary_10_1177_26320843231191645 crossref_primary_10_1186_s12967_017_1174_z crossref_primary_10_3390_cancers12071772 crossref_primary_10_1073_pnas_1802973116 crossref_primary_10_1007_s10555_022_10057_z crossref_primary_10_1186_s12885_024_13395_z crossref_primary_10_1016_j_gene_2017_08_001 crossref_primary_10_3390_diagnostics13040738 crossref_primary_10_1016_j_tranon_2025_102496 crossref_primary_10_1016_j_arcmed_2023_102897 crossref_primary_10_1038_s41467_024_45340_w crossref_primary_10_1186_s12864_023_09571_3 crossref_primary_10_3892_ol_2025_14937 crossref_primary_10_1016_j_future_2024_05_030 crossref_primary_10_3389_fgene_2022_917150 crossref_primary_10_1002_cam4_3240 crossref_primary_10_1136_jitc_2025_012069 crossref_primary_10_1038_s43018_024_00883_1 crossref_primary_10_1016_j_ecoenv_2022_114466 crossref_primary_10_1136_jitc_2019_000110 crossref_primary_10_3389_fonc_2025_1590216 crossref_primary_10_1073_pnas_2002179117 crossref_primary_10_3892_ol_2019_11169 crossref_primary_10_3389_fimmu_2023_1075848 crossref_primary_10_3892_or_2025_8907 crossref_primary_10_1007_s00432_023_05251_7 crossref_primary_10_1093_bib_bbz008 crossref_primary_10_1038_s41598_020_80453_4 crossref_primary_10_1186_s13073_022_01079_x crossref_primary_10_3390_biomedicines10051065 crossref_primary_10_3389_fmolb_2022_806780 crossref_primary_10_1158_1541_7786_MCR_17_0191 crossref_primary_10_1002_jcb_28842 crossref_primary_10_1186_s12935_020_01237_4 crossref_primary_10_3389_fonc_2018_00244 crossref_primary_10_1097_CCO_0000000000000032 crossref_primary_10_1186_s12864_022_08688_1 crossref_primary_10_1016_j_csbj_2024_04_056 crossref_primary_10_3389_fcell_2021_684259 crossref_primary_10_3389_fimmu_2022_1029092 crossref_primary_10_1111_crj_12271 crossref_primary_10_1016_j_jbiotec_2015_02_014 crossref_primary_10_3389_fonc_2020_00468 crossref_primary_10_2217_bmm_2019_0052 crossref_primary_10_1007_s12672_024_01712_8 crossref_primary_10_1080_14737159_2021_1947798 crossref_primary_10_3389_fgene_2021_749850 crossref_primary_10_1186_s12859_023_05210_6 crossref_primary_10_1186_s12885_019_6462_y crossref_primary_10_1002_cam4_4471 crossref_primary_10_4137_CIN_S38000 crossref_primary_10_1109_TCBB_2016_2535267 crossref_primary_10_1097_MD_0000000000035123 crossref_primary_10_1016_j_celrep_2024_114430 crossref_primary_10_1177_00368504211018053 crossref_primary_10_3390_cancers11091251 crossref_primary_10_1007_s00018_023_05034_w crossref_primary_10_1158_1078_0432_CCR_23_2357 crossref_primary_10_1016_j_lungcan_2021_06_020 crossref_primary_10_1186_s12935_018_0610_3 crossref_primary_10_1002_mc_23493 crossref_primary_10_1038_s41598_025_92177_4 crossref_primary_10_1186_s12929_022_00807_0 crossref_primary_10_3390_cancers12123789 crossref_primary_10_3389_fonc_2021_655757 crossref_primary_10_3390_ijms24031897 crossref_primary_10_3109_15419061_2013_876017 crossref_primary_10_1038_s42003_025_07452_x crossref_primary_10_1097_JTO_0000000000000550 crossref_primary_10_1186_s12885_021_08961_8 crossref_primary_10_1093_jnci_djv211 crossref_primary_10_2217_epi_13_62 crossref_primary_10_1098_rsob_150128 crossref_primary_10_1186_s12890_022_02011_0 crossref_primary_10_3389_fcell_2021_655950 crossref_primary_10_1002_jgm_3105 crossref_primary_10_3892_ol_2019_10211 crossref_primary_10_1016_j_heliyon_2024_e34523 crossref_primary_10_1007_s12094_024_03752_6 crossref_primary_10_1038_s41591_019_0595_z crossref_primary_10_1186_s13046_017_0495_3 crossref_primary_10_3389_fphar_2022_874780 crossref_primary_10_1080_19768354_2022_2079718 crossref_primary_10_1097_CJI_0000000000000477 crossref_primary_10_3389_fcell_2022_1067248 crossref_primary_10_5858_arpa_2015_0113_OA crossref_primary_10_1007_s12672_024_01293_6 crossref_primary_10_3389_fmolb_2021_587436 crossref_primary_10_1515_oncologie_2023_0372 crossref_primary_10_1016_j_biopha_2019_01_051 crossref_primary_10_1038_s41419_022_05316_4 crossref_primary_10_1038_s41598_022_14323_6 crossref_primary_10_1186_s12915_024_01866_5 crossref_primary_10_3892_ijo_2019_4953 crossref_primary_10_1186_s12885_020_07473_1 crossref_primary_10_1038_s41598_019_56277_2 crossref_primary_10_1186_s13287_023_03406_4 crossref_primary_10_7554_eLife_98903_4 crossref_primary_10_1016_j_gene_2025_149233 crossref_primary_10_1136_jitc_2023_007935 crossref_primary_10_3389_fimmu_2025_1574434 crossref_primary_10_3390_genes13020238 crossref_primary_10_1155_2021_3219594 crossref_primary_10_3892_ol_2019_10678 crossref_primary_10_1016_j_ymthe_2016_12_018 crossref_primary_10_1038_s41388_018_0645_x crossref_primary_10_1080_14737140_2021_1908132 crossref_primary_10_7554_eLife_75061 crossref_primary_10_1016_j_canlet_2019_12_039 crossref_primary_10_1177_20503121251341114 crossref_primary_10_1371_journal_pcbi_1007869 crossref_primary_10_3390_biology3030578 crossref_primary_10_3389_fpubh_2022_902445 crossref_primary_10_1016_j_compbiomed_2023_106855 crossref_primary_10_3389_fcell_2021_651575 crossref_primary_10_3390_cancers14153630 crossref_primary_10_3390_cancers15215219 crossref_primary_10_1080_15592294_2017_1342912 crossref_primary_10_1007_s11357_024_01442_3 crossref_primary_10_1038_s41598_019_48243_9 crossref_primary_10_1038_sdata_2018_66 crossref_primary_10_3892_or_2024_8694 crossref_primary_10_1038_s41435_024_00289_0 crossref_primary_10_3389_fgene_2022_862977 crossref_primary_10_3892_ol_2019_10563 crossref_primary_10_1097_MD_0000000000030304 crossref_primary_10_1186_s12935_020_01272_1 crossref_primary_10_1016_j_envint_2018_05_007 crossref_primary_10_3390_biomedinformatics5020032 crossref_primary_10_4161_cc_29661 crossref_primary_10_1002_ctm2_70281 crossref_primary_10_1111_apm_13012 crossref_primary_10_2478_rrlm_2019_0001 crossref_primary_10_1016_j_heliyon_2020_e03521 crossref_primary_10_1088_1757_899X_1076_1_012048 crossref_primary_10_1089_sysm_2019_0008 crossref_primary_10_1155_2024_2090450 crossref_primary_10_1186_s12967_020_02545_z crossref_primary_10_3390_biom12020160 crossref_primary_10_1097_HC9_0000000000000659 crossref_primary_10_3892_or_2016_5253 crossref_primary_10_1002_sim_9250 crossref_primary_10_3390_cancers13153875 crossref_primary_10_3390_cells10061409 crossref_primary_10_1093_nar_gkz080 crossref_primary_10_1371_journal_pone_0187287 crossref_primary_10_3389_fgene_2021_746666
ContentType	Journal Article
DBID	CGR CUY CVF ECM EIF NPM 7X8
DOI	10.1126/scitranslmed.3005723
DatabaseName	Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic
DatabaseTitle	MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic
DatabaseTitleList	MEDLINE MEDLINE - Academic
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database
DeliveryMethod	no_fulltext_linktorsrc
Discipline	Medicine
EISSN	1946-6242
ExternalDocumentID	23698379
Genre	Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural
GrantInformation_xml	– fundername: NCI NIH HHS grantid: R01 CA154365
GroupedDBID	--- 0R~ 4.4 53G 7~K ABJNI ACGFS AENEX AJGZS AJWWR ALMA_UNASSIGNED_HOLDINGS BKF C45 CGR CUY CVF DU5 EBS ECM EIF EJD EMOBN F5P HZ~ NPM O9- OFXIZ OVD OVIDX P2P RHI TEORI 7X8
ID	FETCH-LOGICAL-c462t-8eccf46b622dcc4c8a7fd69be1f7e844f8fd19fbd9436f97c4f42c76ffd246532
IEDL.DBID	7X8
ISICitedReferencesCount	440
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000319440500004&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	1946-6242
IngestDate	Fri Sep 05 09:34:06 EDT 2025 Thu Jan 02 22:13:11 EST 2025
IsPeerReviewed	true
IsScholarly	true
Issue	186
Language	English
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c462t-8eccf46b622dcc4c8a7fd69be1f7e844f8fd19fbd9436f97c4f42c76ffd246532
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
PMID	23698379
PQID	1355477625
PQPubID	23479
ParticipantIDs	proquest_miscellaneous_1355477625 pubmed_primary_23698379
PublicationCentury	2000
PublicationDate	2013-05-22
PublicationDateYYYYMMDD	2013-05-22
PublicationDate_xml	– month: 05 year: 2013 text: 2013-05-22 day: 22
PublicationDecade	2010
PublicationPlace	United States
PublicationPlace_xml	– name: United States
PublicationTitle	Science translational medicine
PublicationTitleAlternate	Sci Transl Med
PublicationYear	2013
References	18692272 - Lung Cancer. 2009 Apr;64(1):60-5 18641660 - Nat Med. 2008 Aug;14(8):822-7 8401577 - Nat Genet. 1993 Aug;4(4):332-3 21847063 - J Thorac Oncol. 2011 Aug;6(8):1435-7 23245995 - Cancer Cell. 2013 Jan 14;23(1):9-22 21849417 - Clin Cancer Res. 2011 Oct 1;17 (19):6272-86 22122641 - Epigenomics. 2009 Oct;1(1):153-61 21358745 - Nat Rev Genet. 2011 Apr;12(4):283-93 21430268 - Sci Transl Med. 2011 Mar 23;3(75):75ra25 18295475 - Curr Opin Genet Dev. 2008 Apr;18(2):116-22 22613842 - Genome Res. 2012 Jul;22(7):1197-211 23335087 - CA Cancer J Clin. 2013 Jan;63(1):11-30 17525744 - Oncogene. 2007 Nov 1;26(50):7170-4 18781170 - Br J Cancer. 2008 Oct 7;99(7):1083-8 21593595 - Epigenetics. 2011 Jun;6(6):692-702 17334365 - Nat Genet. 2007 Apr;39(4):457-66 17339880 - Nat Rev Genet. 2007 Apr;8(4):286-98 17632057 - Cell. 2007 Jul 13;130(1):77-88 17512414 - Cell. 2007 May 18;129(4):823-37 16034368 - Nat Rev Cancer. 2005 Aug;5(8):615-25 16287078 - Int J Cancer. 2006 Apr 15;118(8):1922-9 19010856 - Clin Cancer Res. 2008 Nov 15;14(22):7397-404 21074720 - Dev Cell. 2010 Nov 16;19(5):698-711 20961245 - N Engl J Med. 2010 Oct 21;363(17):1621-30 19536264 - Nature. 2009 Jun 18;459(7249):987-91 20465387 - Future Oncol. 2010 May;6(5):717-32 9743292 - Br J Cancer. 1998 Sep;78(6):739-44 20421987 - PLoS One. 2010 Apr 22;5(4):e10312 14659893 - Gene. 2003 Dec 24;323:189-99 18054408 - Lung Cancer. 2008 Jun;60(3):374-80 17320506 - Cell. 2007 Feb 23;128(4):683-92 16953229 - Oncogene. 2007 Feb 15;26(7):1098-100
References_xml	– reference: 21849417 - Clin Cancer Res. 2011 Oct 1;17 (19):6272-86 – reference: 17339880 - Nat Rev Genet. 2007 Apr;8(4):286-98 – reference: 8401577 - Nat Genet. 1993 Aug;4(4):332-3 – reference: 17320506 - Cell. 2007 Feb 23;128(4):683-92 – reference: 18641660 - Nat Med. 2008 Aug;14(8):822-7 – reference: 21847063 - J Thorac Oncol. 2011 Aug;6(8):1435-7 – reference: 21430268 - Sci Transl Med. 2011 Mar 23;3(75):75ra25 – reference: 16034368 - Nat Rev Cancer. 2005 Aug;5(8):615-25 – reference: 19010856 - Clin Cancer Res. 2008 Nov 15;14(22):7397-404 – reference: 21593595 - Epigenetics. 2011 Jun;6(6):692-702 – reference: 16953229 - Oncogene. 2007 Feb 15;26(7):1098-100 – reference: 17632057 - Cell. 2007 Jul 13;130(1):77-88 – reference: 23245995 - Cancer Cell. 2013 Jan 14;23(1):9-22 – reference: 14659893 - Gene. 2003 Dec 24;323:189-99 – reference: 21358745 - Nat Rev Genet. 2011 Apr;12(4):283-93 – reference: 16287078 - Int J Cancer. 2006 Apr 15;118(8):1922-9 – reference: 21074720 - Dev Cell. 2010 Nov 16;19(5):698-711 – reference: 18054408 - Lung Cancer. 2008 Jun;60(3):374-80 – reference: 22613842 - Genome Res. 2012 Jul;22(7):1197-211 – reference: 17525744 - Oncogene. 2007 Nov 1;26(50):7170-4 – reference: 9743292 - Br J Cancer. 1998 Sep;78(6):739-44 – reference: 18692272 - Lung Cancer. 2009 Apr;64(1):60-5 – reference: 17512414 - Cell. 2007 May 18;129(4):823-37 – reference: 18781170 - Br J Cancer. 2008 Oct 7;99(7):1083-8 – reference: 23335087 - CA Cancer J Clin. 2013 Jan;63(1):11-30 – reference: 19536264 - Nature. 2009 Jun 18;459(7249):987-91 – reference: 18295475 - Curr Opin Genet Dev. 2008 Apr;18(2):116-22 – reference: 20961245 - N Engl J Med. 2010 Oct 21;363(17):1621-30 – reference: 22122641 - Epigenomics. 2009 Oct;1(1):153-61 – reference: 20421987 - PLoS One. 2010 Apr 22;5(4):e10312 – reference: 17334365 - Nat Genet. 2007 Apr;39(4):457-66 – reference: 20465387 - Future Oncol. 2010 May;6(5):717-32
SSID	ssj0068356
Score	2.5760245
Snippet	Activation of normally silent tissue-specific genes and the resulting cell "identity crisis" are the unexplored consequences of malignant epigenetic...
SourceID	proquest pubmed
SourceType	Aggregation Database Index Database
StartPage	186ra66
SubjectTerms	Animals Cell Line, Tumor DNA Methylation - genetics Epigenesis, Genetic Female Gene Expression Regulation, Neoplastic Germ Cells - metabolism Humans Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - pathology Neoplasm Invasiveness Neoplasm Metastasis - genetics Neoplasm Staging Organ Specificity Placenta - metabolism Pregnancy Prognosis Promoter Regions, Genetic - genetics Reproducibility of Results Transcriptome
Title	Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers
URI	https://www.ncbi.nlm.nih.gov/pubmed/23698379 https://www.proquest.com/docview/1355477625
Volume	5
WOSCitedRecordID	wos000319440500004&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings	1
isFullTextHit
isPrint
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8QwEA7qinjx_X4QwWvUpmkeJxFRPLjLHlT2tqRJsyys23Vb_f3OpFVPguCllEJoSL7MTGbmmyHkXMbkQY_gFRkTIdFMpz4wiymFTtqMR2fOy6Pq9fRgYPqtw61q0yq_ZGIU1L506CO_TFAxKji62fXsjWHXKIyuti00FkknBVMGUa0G31EECdZFZBcZIRnyIFrqXEuaqVEZTEDnXGDJdoUNi34zMqOyuV__7zQ3yFprZtKbBhebZKGYbpGVbhtI3ybhztXlbOwo8hoarywtAx2BnEa7k9qppzFdC8mS8BkEIh37JrMIXu0oXtNBUtLXorZgYVbjisFUYegExAd1CKZ5tUOe7--ebh9Y23KBOSF5zTTsaBAyl5x754TTVgUvTV4kQRVaiKCDT0zIvRGpDEY5EQR3SobgOVZq47tkaQr_2idUaZsXWto85VakeZJLnYkivbKpz4zO-AE5-1rBIUAa4xR2WpTv1fBnDQ_IXrMNw1lTe2PIU2ngTm0O_zD6iKzy2LwiY5wfk06AA12ckGX3UY-r-WnECjx7_e4nTCTL9w
linkProvider	ProQuest
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Ectopic+activation+of+germline+and+placental+genes+identifies+aggressive+metastasis-prone+lung+cancers&rft.jtitle=Science+translational+medicine&rft.au=Rousseaux%2C+Sophie&rft.au=Debernardi%2C+Alexandra&rft.au=Jacquiau%2C+Baptiste&rft.au=Vitte%2C+Anne-Laure&rft.date=2013-05-22&rft.eissn=1946-6242&rft.volume=5&rft.issue=186&rft.spage=186ra66&rft_id=info:doi/10.1126%2Fscitranslmed.3005723&rft_id=info%3Apmid%2F23698379&rft_id=info%3Apmid%2F23698379&rft.externalDocID=23698379
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1946-6242&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1946-6242&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1946-6242&client=summon