An unexplored consequence of epigenetic alterations associated with cancer is the ectopic expression of tissue-restricted genes. Here, a new strategy was developed to decipher genome-wide expression data in search for these off-context gene activations, which consisted first, in identifying a large number of tissue-specific genes normally epigenetically silenced in most somatic cells and second, in using them as cancer biomarkers on an on/off basis. Applying this concept to analyze whole-genome transcriptome data in lung cancer, we discovered a specific group of 26 genes whose expression was a strong and independent predictor of poor prognosis in our cohort of 293 lung tumours, as well as in two independent external populations. In addition, these 26 classifying genes enabled us to isolate a homogenous group of metastatic-prone highly aggressive tumours, whose characteristic gene expression profile revealed a high proliferative potential combined to a significant decrease in immune and signaling functions. This work illustrates a new approach for a personalized management of cancer, with applications to any cancer type.
Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers.
Sex, Specimen part
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Bromodomain-dependent stage-specific male genome programming by Brdt.
Specimen part
View SamplesMale germ cell differentiation is a highly regulated multistep process initiated by the commitment of progenitor cells into meiosis and characterized by major chromatin reorganizations in haploid spermatids. We report here that a single member of the double bromodomain BET factors, Brdt, is a master regulator of both meiotic divisions and post-meiotic genome repackaging. Upon its activation at the onset of meiosis, Brdt drives and determines the developmental timing of a testis-specific gene expression program. In meiotic cells, Brdt initiates a genuine histone acetylation-guided programming of the genome by activating essential meiotic genes and repressing a progenitor cells gene expression program, while priming a post-meiotic gene group for further activation. At post-meiotic stages, a global chromatin hyperacetylation gives the signal for Brdts first bromodomain to direct the genome-wide replacement of histones by transition proteins. Brdt is therefore a unique and essential regulator of male germ cell differentiation, which, by using various domains in a developmentally controlled manner, first drives a specific spermatogenic gene expression program, and later controls the tight packaging of the male genome.
Bromodomain-dependent stage-specific male genome programming by Brdt.
No sample metadata fields
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Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
Specimen part
View SamplesAlthough the conserved AAA ATPase bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics and RNA-seq experiments in embryonic stem cells, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells, Atad2 becomes critical in sustaining specific gene expression programs, controlling proliferation and differentiation. Altogether, this work defines Atad2s function as a facilitator of general chromatin-templated activities such as transcription.
Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
Specimen part
View SamplesChromosome 1 pericentric heterochromatin rearrangements : potent drivers of nuclear architecture perturbations and gene deregulation in human B cell lymphoma
No associated publication
Cell line
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No associated publication
Specimen part, Time
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Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.
Sex, Age
View SamplesTranscriptomic response of tumoral and normal brain tissue, treated with the MRT irradiation or the BB irradiation, after 6 h, 48 h, 8 days, 15 days, using Affymetrix GeneChip Rat 230_ 2.
No associated publication
Specimen part, Treatment, Time
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Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
Sex, Age, Specimen part, Subject
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