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...

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Vydáno v:	Science translational medicine Ročník 5; číslo 186; s. 186ra66
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 22.05.2013
Témata:	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
On-line přístup:	Zjistit podrobnosti o přístupu
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

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
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Snippet	Activation of normally silent tissue-specific genes and the resulting cell "identity crisis" are the unexplored consequences of malignant epigenetic...
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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
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