1. A Landscape of Pharmacogenomic Interactions in Cancer.

    Cell 166(3):740 (2016) PMID 27397505 PMCID PMC4967469

    Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature of cancer. Using this information to guide the development and application of therapies in the clinic is challenging. Here, we report how cancer-driven alterations identified in 11,289 tumors from...
  2. Dual role of Med12 in PRC1-dependent gene repression and ncRNA-mediated transcriptional activation.

    Cell Cycle 15(11):1479 (2016) PMID 27096886 PMCID PMC4934080

    Mediator is considered an enhancer of RNA-Polymerase II dependent transcription but its function and regulation in pluripotent mouse embryonic stem cells (mESCs) remains unresolved. One means of controlling the function of Mediator is provided by the binding of the Cdk8 module (Med12, Cdk8, Ccnc...
  3. Epigenomic analysis detects aberrant super-enhancer DNA methylation in human cancer.

    Genome Biology 17(1):11 (2016) PMID 26813288 PMCID PMC4728783

    One of the hallmarks of cancer is the disruption of gene expression patterns. Many molecular lesions contribute to this phenotype, and the importance of aberrant DNA methylation profiles is increasingly recognized. Much of the research effort in this area has examined proximal promoter regions a...
  4. DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma.

    Hepatology 61(6):1945 (2015) PMID 25645722

    Epigenetic deregulation has emerged as a driver in human malignancies. There is no clear understanding of the epigenetic alterations in hepatocellular carcinoma (HCC) and of the potential role of DNA methylation markers as prognostic biomarkers. Analysis of tumor tissue from 304 patients with HC...
  5. Head-to-head antisense transcription and R-loop formation promotes transcriptional activation.

    PNAS 112(18):5785 (2015) PMID 25902512 PMCID PMC4426458

    The mechanisms used by antisense transcripts to regulate their corresponding sense mRNAs are not fully understood. Herein, we have addressed this issue for the vimentin (VIM) gene, a member of the intermediate filament family involved in cell and tissue integrity that is deregulated in different...
  6. Unique genomic profile of fibrolamellar hepatocellular carcinoma.

    Gastroenterology 148(4):806 (2015) PMID 25557953 PMCID PMC4521774

    Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary hepatic cancer that develops in children and young adults without cirrhosis. Little is known about its pathogenesis, and it can be treated only with surgery. We performed an integrative genomic analysis of a large series of patients ...
  7. A DNA methylation-based definition of biologically distinct breast cancer subtypes.

    Molecular Oncology 9(3):555 (2015) PMID 25468711

    In cancer, epigenetic states are deregulated and thought to be of significance in cancer development and progression. We explored DNA methylation-based signatures in association with breast cancer subtypes to assess their impact on clinical presentation and patient prognosis. DNA methylation was...
  8. The DNA methylation drift of the atherosclerotic aorta increases with lesion progression.

    BMC Medical Genomics 8(1):7 (2015) PMID 25881171 PMCID PMC4353677

    Atherosclerosis severity-independent alterations in DNA methylation, a reversible and highly regulated DNA modification, have been detected in aortic atheromas, thus supporting the hypothesis that epigenetic mechanisms participate in the pathogenesis of atherosclerosis. One yet unaddressed issue...
  9. Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.
    Ignacio Blanco, Karoline Kuchenbaecker, Daniel Cuadras, Xianshu Wang, Daniel Barrowdale, Gorka Ruiz de Garibay, Pablo Librado, Alejandro Sánchez-Gracia, Julio Rozas, Núria Bonifaci, Lesley McGuffog, Vernon S Pankratz, Abul Islam, Francesca Mateo, Antoni Berenguer, Anna Petit, Isabel Català, Joan Brunet, Lidia Feliubadaló, Eva Tornero, Javier Benítez, Ana Osorio, Teresa Ramón y Cajal, Heli Nevanlinna, Kristiina Aittomäki, Banu K Arun, Amanda E Toland, Beth Y Karlan, Christine Walsh, Jenny Lester, Mark H Greene, Phuong L Mai, Robert L Nussbaum, Irene L Andrulis, Susan M Domchek, Katherine L Nathanson, Timothy Rebbeck, Rosa Barkardottir, Anna Jakubowska, Jan Lubinski, Katarzyna Durda, Katarzyna Jaworska-Bieniek, Kathleen Claes, Tom Van Maerken, Orland Díez, Thomas V Hansen, Lars Jønson, Anne-Marie Gerdes, Bent Ejlertsen, Miguel de la Hoya, Trinidad Caldés, Alison M Dunning, Clare Oliver, Elena Fineberg, Margaret Cook, Susan Peock, Emma McCann, Alex Murray, Chris Jacobs, Gabriella Pichert, Fiona Lalloo, Carol Chu, Huw Dorkins, Joan Paterson, Kai-Ren Ong, Manuel R Teixeira, Frans B L Hogervorst, Annemarie van der Hout, Caroline Seynaeve, Rob B van der Luijt, Marjolijn J Ligtenberg, Peter Devilee, Juul T Wijnen, Matti A Rookus, Hanne E J Meijers-Heijboer, Marinus J Blok, Ans M W van den Ouweland, Cora M Aalfs, Gustavo C Rodriguez, Kelly-Anne A Phillips, Marion Piedmonte, Stacy R Nerenstone, Victoria L Bae-Jump, David M O'Malley, Elena S Ratner, Rita K Schmutzler, Barbara Wappenschmidt, Kerstin Rhiem, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Hansjoerg J Plendl, Dieter Niederacher, Christian Sutter, Shan Wang-Gohrke, Doris Steinemann, Sabine Preisler-Adams, Karin Kast, Raymonda Varon-Mateeva, Andrea Gehrig, Anders Bojesen, Inge Sokilde Pedersen, Lone Sunde, Uffe Birk Jensen, Mads Thomassen, Torben A Kruse, Lenka Foretova, Paolo Peterlongo, Loris Bernard, Bernard Peissel, Giulietta Scuvera, Siranoush Manoukian, Paolo Radice, Laura Ottini, Marco Montagna, Simona Agata, Christine Maugard, Jacques Simard, Penny Soucy, Andreas Berger, Anneliese Fink-Retter, Christian F Singer, Christine Rappaport, Daphne Geschwantler-Kaulich, Muy-Kheng Tea, Georg Pfeiler, Esther M John, Alex Miron, Susan L Neuhausen, Mary Beth Terry, Wendy K Chung, Mary B Daly, David E Goldgar, Ramunas Janavicius, Cecilia M Dorfling, Elisabeth J van Rensburg, Florentia Fostira, Irene Konstantopoulou, Judy Garber, Andrew K Godwin, Edith Olah, Steven A Narod, Gad Rennert, Shani Shimon Paluch, Yael Laitman, Eitan Friedman, Annelie Liljegren, Johanna Rantala, Marie Stenmark-Askmalm, Niklas Loman, Evgeny N Imyanitov, Ute Hamann, Amanda B Spurdle, Sue Healey, Jeffrey N Weitzel, Josef Herzog, David Margileth, Chiara Gorrini, Manel Esteller, Antonio Gómez, Sergi Sayols, Enrique Vidal, Holger Heyn, Dominique Stoppa-Lyonnet, Melanie Léoné, Laure Barjhoux, Marion Fassy-Colcombet, Antoine de Pauw, Christine Lasset, Sandra Fert Ferrer, Laurent Castera, Pascaline Berthet, François Cornelis, Yves-Jean Bignon, Francesca Damiola, Sylvie Mazoyer, Olga M Sinilnikova, Christopher A Maxwell, Joseph Vijai, Mark Robson, Noah Kauff, Marina J Corines, Danylko Villano, Julie Cunningham, Adam Lee, Noralane Lindor, Conxi Lázaro, Douglas F Easton, Kenneth Offit, Georgia Chenevix-Trench, Fergus J Couch, Antonis C Antoniou, and Miguel Angel Pujana

    PLoS ONE 10(4):e0120020 (2015) PMID 25830658 PMCID PMC4382299

    While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between...
  10. DNA methylation map of human atherosclerosis.

    Circulation: Cardiovascular Genetics 7(5):692 (2014) PMID 25091541

    Epigenetic alterations may contribute to the development of atherosclerosis. In particular, DNA methylation, a reversible and highly regulated DNA modification, could influence disease onset and progression because it functions as an effector for environmental influences, including diet and life...
  11. A comprehensive DNA methylation profile of epithelial-to-mesenchymal transition.

    Cancer Research 74(19):5608 (2014) PMID 25106427

    Epithelial-to-mesenchymal transition (EMT) is a plastic process in which fully differentiated epithelial cells are converted into poorly differentiated, migratory and invasive mesenchymal cells, and it has been related to the metastasis potential of tumors. This is a reversible process and cells...
  12. Linkage of DNA methylation quantitative trait loci to human cancer risk.

    Cell Reports 7(2):331 (2014) PMID 24703846

    Epigenetic regulation and, in particular, DNA methylation have been linked to the underlying genetic sequence. DNA methylation quantitative trait loci (meQTL) have been identified through significant associations between the genetic and epigenetic codes in physiological and pathological contexts...
  13. A prognostic DNA methylation signature for stage I non-small-cell lung cancer.

    Journal of Clinical Oncology 31(32):4140 (2013) PMID 24081945

    Non-small-cell lung cancer (NSCLC) is a tumor in which only small improvements in clinical outcome have been achieved. The issue is critical for stage I patients for whom there are no available biomarkers that indicate which high-risk patients should receive adjuvant chemotherapy. We aimed to fi...
  14. DNA methylation contributes to natural human variation.

    Genome Research 23(9):1363 (2013) PMID 23908385 PMCID PMC3759714

    DNA methylation patterns are important for establishing cell, tissue, and organism phenotypes, but little is known about their contribution to natural human variation. To determine their contribution to variability, we have generated genome-scale DNA methylation profiles of three human populatio...
  15. Dysregulation of the long non-coding RNA transcriptome in a Rett syndrome mouse model.

    RNA Biology 10(7):1197 (2013) PMID 23611944 PMCID PMC3849168

    Mecp2 is a transcriptional repressor protein that is mutated in Rett syndrome, a neurodevelopmental disorder that is the second most common cause of mental retardation in women. It has been shown that the loss of the Mecp2 protein in Rett syndrome cells alters the transcriptional silencing of co...
  16. DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker.

    Carcinogenesis 34(1):102 (2013) PMID 23054610 PMCID PMC3534196

    Using whole blood from 15 twin pairs discordant for breast cancer and high-resolution (450K) DNA methylation analysis, we identified 403 differentially methylated CpG sites including known and novel potential breast cancer genes. Confirming the results in an independent validation cohort of 21 t...
  17. Distinct DNA methylomes of newborns and centenarians.

    PNAS 109(26):10522 (2012) PMID 22689993 PMCID PMC3387108

    Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian ...
  18. Whole-genome bisulfite DNA sequencing of a DNMT3B mutant patient.

    Epigenetics 7(6):542 (2012) PMID 22595875 PMCID PMC3398983

    The immunodeficiency, centromere instability and facial anomalies (ICF) syndrome is associated to mutations of the DNA methyl-transferase DNMT3B, resulting in a reduction of enzyme activity. Aberrant expression of immune system genes and hypomethylation of pericentromeric regions accompanied by ...
  19. Novel insights into DNA methylation features in spermatozoa: stability and peculiarities.

    PLoS ONE 7(10):e44479 (2012) PMID 23071498 PMCID PMC3467000

    Data about the entire sperm DNA methylome are limited to two sperm donors whereas studies dealing with a greater number of subjects focused only on a few genes or were based on low resolution arrays. This implies that information about what we can consider as a normal sperm DNA methylome and whe...
  20. Epigenetic disruption of the PIWI pathway in human spermatogenic disorders.

    PLoS ONE 7(10):e47892 (2012) PMID 23112866 PMCID PMC3480440

    Epigenetic changes are involved in a wide range of common human diseases. Although DNA methylation defects are known to be associated with male infertility in mice, their impact on human deficiency of sperm production has yet to be determined. We have assessed the global genomic DNA methylation ...