Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2011-06-07
    Description: Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322590/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322590/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Puente, Xose S -- Pinyol, Magda -- Quesada, Victor -- Conde, Laura -- Ordonez, Gonzalo R -- Villamor, Neus -- Escaramis, Georgia -- Jares, Pedro -- Bea, Silvia -- Gonzalez-Diaz, Marcos -- Bassaganyas, Laia -- Baumann, Tycho -- Juan, Manel -- Lopez-Guerra, Monica -- Colomer, Dolors -- Tubio, Jose M C -- Lopez, Cristina -- Navarro, Alba -- Tornador, Cristian -- Aymerich, Marta -- Rozman, Maria -- Hernandez, Jesus M -- Puente, Diana A -- Freije, Jose M P -- Velasco, Gloria -- Gutierrez-Fernandez, Ana -- Costa, Dolors -- Carrio, Anna -- Guijarro, Sara -- Enjuanes, Anna -- Hernandez, Lluis -- Yague, Jordi -- Nicolas, Pilar -- Romeo-Casabona, Carlos M -- Himmelbauer, Heinz -- Castillo, Ester -- Dohm, Juliane C -- de Sanjose, Silvia -- Piris, Miguel A -- de Alava, Enrique -- San Miguel, Jesus -- Royo, Romina -- Gelpi, Josep L -- Torrents, David -- Orozco, Modesto -- Pisano, David G -- Valencia, Alfonso -- Guigo, Roderic -- Bayes, Monica -- Heath, Simon -- Gut, Marta -- Klatt, Peter -- Marshall, John -- Raine, Keiran -- Stebbings, Lucy A -- Futreal, P Andrew -- Stratton, Michael R -- Campbell, Peter J -- Gut, Ivo -- Lopez-Guillermo, Armando -- Estivill, Xavier -- Montserrat, Emili -- Lopez-Otin, Carlos -- Campo, Elias -- 088340/Wellcome Trust/United Kingdom -- 093867/Wellcome Trust/United Kingdom -- England -- Nature. 2011 Jun 5;475(7354):101-5. doi: 10.1038/nature10113.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21642962" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Carrier Proteins/genetics ; DNA Mutational Analysis ; Genome, Human/*genetics ; Humans ; Karyopherins/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/*genetics ; Molecular Sequence Data ; Mutation/*genetics ; Myeloid Differentiation Factor 88/chemistry/genetics ; Receptor, Notch1/genetics ; Receptors, Cytoplasmic and Nuclear/genetics ; Reproducibility of Results
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2015-07-23
    Description: Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3' region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to 〉/=4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Puente, Xose S -- Bea, Silvia -- Valdes-Mas, Rafael -- Villamor, Neus -- Gutierrez-Abril, Jesus -- Martin-Subero, Jose I -- Munar, Marta -- Rubio-Perez, Carlota -- Jares, Pedro -- Aymerich, Marta -- Baumann, Tycho -- Beekman, Renee -- Belver, Laura -- Carrio, Anna -- Castellano, Giancarlo -- Clot, Guillem -- Colado, Enrique -- Colomer, Dolors -- Costa, Dolors -- Delgado, Julio -- Enjuanes, Anna -- Estivill, Xavier -- Ferrando, Adolfo A -- Gelpi, Josep L -- Gonzalez, Blanca -- Gonzalez, Santiago -- Gonzalez, Marcos -- Gut, Marta -- Hernandez-Rivas, Jesus M -- Lopez-Guerra, Monica -- Martin-Garcia, David -- Navarro, Alba -- Nicolas, Pilar -- Orozco, Modesto -- Payer, Angel R -- Pinyol, Magda -- Pisano, David G -- Puente, Diana A -- Queiros, Ana C -- Quesada, Victor -- Romeo-Casabona, Carlos M -- Royo, Cristina -- Royo, Romina -- Rozman, Maria -- Russinol, Nuria -- Salaverria, Itziar -- Stamatopoulos, Kostas -- Stunnenberg, Hendrik G -- Tamborero, David -- Terol, Maria J -- Valencia, Alfonso -- Lopez-Bigas, Nuria -- Torrents, David -- Gut, Ivo -- Lopez-Guillermo, Armando -- Lopez-Otin, Carlos -- Campo, Elias -- England -- Nature. 2015 Oct 22;526(7574):519-24. doi: 10.1038/nature14666. Epub 2015 Jul 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain. ; Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain. ; Unitat de Hematologia, Hospital Clinic, IDIBAPS, Universitat de Barcelona, 08036 Barcelona, Spain. ; Departament d'Anatomia Patologica, Microbiologia i Farmacologia, Universitat de Barcelona, 08036 Barcelona, Spain. ; Programa Conjunto de Biologia Computacional, Barcelona Supercomputing Center (BSC), Institut de Recerca Biomedica (IRB), Spanish National Bioinformatics Institute, Universitat de Barcelona, 08028 Barcelona, Spain. ; Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain. ; Unidad de Genomica, IDIBAPS, 08036 Barcelona, Spain. ; Servicio de Hematologia, Hospital Clinic, IDIBAPS, 08036 Barcelona, Spain. ; Institute for Cancer Genetics, Columbia University, New York 10032, USA. ; Servicio de Hematologia, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain. ; Center for Genomic Regulation (CRG), Pompeu Fabra University (UPF), Hospital del Mar Research Institute (IMIM), 08003 Barcelona, Spain. ; Servicio de Hematologia, IBSAL-Hospital Universitario de Salamanca, Centro de Investigacion del Cancer, Universidad de Salamanca-CSIC, 37007 Salamanca, Spain. ; Centro Nacional de Analisis Genomico, Parc Cientific de Barcelona, 08028 Barcelona, Spain. ; Catedra Inter-Universitaria de Derecho y Genoma Humano, Universidad de Deusto, Universidad del Pais Vasco, 48007 Bilbao, Spain. ; Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Spanish National Bioinformatics Institute, 28029 Madrid, Spain. ; Institute of Applied Biosciences, Center for Research and Technology Hellas, 57001 Thermi, Thessaloniki, Greece. ; Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, 6500 HB Nijmegen, The Netherlands. ; Servicio de Hematologia, Hospital Clinico de Valencia, 46010 Valencia, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26200345" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics ; Alternative Splicing/genetics ; B-Cell-Specific Activator Protein/biosynthesis/genetics ; B-Lymphocytes/metabolism ; Carrier Proteins/genetics ; Chromosomes, Human, Pair 9/genetics ; DNA Mutational Analysis ; DNA, Neoplasm/genetics ; Enhancer Elements, Genetic/genetics ; Genomics ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/*genetics/metabolism/pathology ; Mutation/*genetics ; Nerve Tissue Proteins/genetics ; Nuclear Proteins/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics ; Receptor, Notch1/genetics/metabolism ; Transcription Factors/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...