Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Zur Ergebnisliste
Open Access
    Datensatz exportieren als...
  • BibTeX
Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer
Nature genetics, 2012-10, Vol.44 (10), p.1104-1110
2012

Details

Autor(en) / Beteiligte
Titel
Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer
Ist Teil von
  • Nature genetics, 2012-10, Vol.44 (10), p.1104-1110
Ort / Verlag
New York, NY: Nature Publishing Group
Erscheinungsjahr
2012
Link zum Volltext
Beschreibungen/Notizen
  • Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis. We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4±1 protein-changing mutations per million base pairs. Therefore, we conducted integrated analyses of the various data sets to identify pathogenetically relevant mutated genes. In all cases, we found evidence for inactivation of TP53 and RB1 and identified recurrent mutations in the CREBBP, EP300 and MLL genes that encode histone modifiers. Furthermore, we observed mutations in PTEN, SLIT2 and EPHA7, as well as focal amplifications of the FGFR1 tyrosine kinase gene. Finally, we detected many of the alterations found in humans in SCLC tumors from Tp53 and Rb1 double knockout mice. Our study implicates histone modification as a major feature of SCLC, reveals potentially therapeutically tractable genomic alterations and provides a generalizable framework for the identification of biologically relevant genes in the context of high mutational background.
Sprache
Englisch
Identifikatoren
ISSN: 1061-4036
eISSN: 1546-1718
DOI: 10.1038/ng.2396
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4915822
Format
–
Schlagworte
Amino Acid Substitution, Animals, Biological and medical sciences, Cell Line, Tumor, CREB-Binding Protein - genetics, Diagnosis, DNA Copy Number Variations, DNA Mutational Analysis, E1A-Associated p300 Protein - genetics, Fundamental and applied biological sciences. Psychology, Gene Expression Profiling, Gene mutations, Gene Regulatory Networks, Genetic aspects, Genetics, Genetics of eukaryotes. Biological and molecular evolution, Genome, Human, Genome-Wide Association Study, Histone-Lysine N-Methyltransferase, Humans, Intercellular Signaling Peptides and Proteins - genetics, Life Sciences, Lung cancer, Lung cancer, Small cell, Lung Neoplasms - genetics, Medical research, Mice, Mice, Knockout, Models, Molecular, Mutation, Myeloid-Lymphoid Leukemia Protein - genetics, Nerve Tissue Proteins - genetics, Oligonucleotide Array Sequence Analysis, Physiological aspects, Polymorphism, Single Nucleotide, Protein Processing, Post-Translational - genetics, PTEN Phosphohydrolase - genetics, Retinoblastoma Protein - genetics, Risk factors, Small Cell Lung Carcinoma - genetics, Tumor Suppressor Protein p53 - genetics, Tumors

Weiterführende Literatur

Empfehlungen zum selben Thema automatisch vorgeschlagen von bX