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Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

(2012) NATURE GENETICS. 44(10). p.1104-1110
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Abstract
Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). 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(4). 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.
Keywords
PROSTATE-CANCER, EGFR MUTATIONS, FREQUENT MUTATION, NEUROENDOCRINE TUMORS, ACUTE LYMPHOBLASTIC-LEUKEMIA, MOUSE MODEL, P53 REGULATION, EPH-RECEPTOR, E-CADHERIN, GENE

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Citation

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MLA
Peifer, Martin, Lynnette Fernández-Cuesta, Martin L Sos, et al. “Integrative Genome Analyses Identify Key Somatic Driver Mutations of Small-cell Lung Cancer.” NATURE GENETICS 44.10 (2012): 1104–1110. Print.
APA
Peifer, M., Fernández-Cuesta, L., Sos, M. L., George, J., Seidel, D., Kasper, L. H., Plenker, D., et al. (2012). Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. NATURE GENETICS, 44(10), 1104–1110.
Chicago author-date
Peifer, Martin, Lynnette Fernández-Cuesta, Martin L Sos, Julie George, Danila Seidel, Lawryn H Kasper, Dennis Plenker, et al. 2012. “Integrative Genome Analyses Identify Key Somatic Driver Mutations of Small-cell Lung Cancer.” Nature Genetics 44 (10): 1104–1110.
Chicago author-date (all authors)
Peifer, Martin, Lynnette Fernández-Cuesta, Martin L Sos, Julie George, Danila Seidel, Lawryn H Kasper, Dennis Plenker, Frauke Leenders, Ruping Sun, Thomas Zander, Roopika Menon, Mirjam Koker, Ilona Dahmen, Christian Müller, Vincenzo Di Cerbo, Hans-Ulrich Schildhaus, Janine Altmüller, Ingelore Baessmann, Christian Becker, Bram De Wilde, Jo Vandesompele, Diana Böhm, Sascha Ansén, Franziska Gabler, Ines Wilkening, Stefanie Heynck, Johannes M Heuckmann, Xin Lu, Scott L Carter, Kristian Cibulskis, Shantanu Banerji, Gad Getz, Kwon-Sik Park, Daniel Rauh, Christian Grütter, Matthias Fischer, Laura Pasqualucci, Gavin Wright, Zoe Wainer, Prudence Russell, Iver Petersen, Yuan Chen, Erich Stoelben, Corinna Ludwig, Philipp Schnabel, Hans Hoffmann, Thomas Muley, Michael Brockmann, Walburga Engel-Riedel, Lucia A Muscarella, Vito M Fazio, Harry Groen, Wim Timens, Hannie Sietsma, Erik Thunnissen, Egbert Smit, Daniëlle AM Heideman, Peter JF Snijders, Federico Cappuzzo, Claudia Ligorio, Stefania Damiani, John Field, Steinar Solberg, Odd Terje Brustugun, Marius Lund-Iversen, Jörg Sänger, Joachim H Clement, Alex Soltermann, Holger Moch, Walter Weder, Benjamin Solomon, Jean-Charles Soria, Pierre Validire, Benjamin Besse, Elisabeth Brambilla, Christian Brambilla, Sylvia Lantuejoul, Philippe Lorimier, Peter M Schneider, Michael Hallek, William Pao, Matthew Meyerson, Julien Sage, Jay Shendure, Robert Schneider, Reinhard Büttner, Jürgen Wolf, Peter Nürnberg, Sven Perner, Lukas C Heukamp, Paul K Brindle, Stefan Haas, and Roman K Thomas. 2012. “Integrative Genome Analyses Identify Key Somatic Driver Mutations of Small-cell Lung Cancer.” Nature Genetics 44 (10): 1104–1110.
Vancouver
1.
Peifer M, Fernández-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. NATURE GENETICS. 2012;44(10):1104–10.
IEEE
[1]
M. Peifer et al., “Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer,” NATURE GENETICS, vol. 44, no. 10, pp. 1104–1110, 2012.
@article{3171598,
  abstract     = {Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). 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(4). 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.},
  author       = {Peifer, Martin and Fernández-Cuesta, Lynnette and Sos, Martin L and George, Julie and Seidel, Danila and Kasper, Lawryn H and Plenker, Dennis and Leenders, Frauke and Sun, Ruping and Zander, Thomas and Menon, Roopika and Koker, Mirjam and Dahmen, Ilona and Müller, Christian and Di Cerbo, Vincenzo and Schildhaus, Hans-Ulrich and Altmüller, Janine and Baessmann, Ingelore and Becker, Christian and De Wilde, Bram and Vandesompele, Jo and Böhm, Diana and Ansén, Sascha and Gabler, Franziska and Wilkening, Ines and Heynck, Stefanie and Heuckmann, Johannes M and Lu, Xin and Carter, Scott L and Cibulskis, Kristian and Banerji, Shantanu and Getz, Gad and Park, Kwon-Sik and Rauh, Daniel and Grütter, Christian and Fischer, Matthias and Pasqualucci, Laura and Wright, Gavin and Wainer, Zoe and Russell, Prudence and Petersen, Iver and Chen, Yuan and Stoelben, Erich and Ludwig, Corinna and Schnabel, Philipp and Hoffmann, Hans and Muley, Thomas and Brockmann, Michael and Engel-Riedel, Walburga and Muscarella, Lucia A and Fazio, Vito M and Groen, Harry and Timens, Wim and Sietsma, Hannie and Thunnissen, Erik and Smit, Egbert and Heideman, Daniëlle AM and Snijders, Peter JF and Cappuzzo, Federico and Ligorio, Claudia and Damiani, Stefania and Field, John and Solberg, Steinar and Brustugun, Odd Terje and Lund-Iversen, Marius and Sänger, Jörg and Clement, Joachim H and Soltermann, Alex and Moch, Holger and Weder, Walter and Solomon, Benjamin and Soria, Jean-Charles and Validire, Pierre and Besse, Benjamin and Brambilla, Elisabeth and Brambilla, Christian and Lantuejoul, Sylvia and Lorimier, Philippe and Schneider, Peter M and Hallek, Michael and Pao, William and Meyerson, Matthew and Sage, Julien and Shendure, Jay and Schneider, Robert and Büttner, Reinhard and Wolf, Jürgen and Nürnberg, Peter and Perner, Sven and Heukamp, Lukas C and Brindle, Paul K and Haas, Stefan and Thomas, Roman K},
  issn         = {1061-4036},
  journal      = {NATURE GENETICS},
  keywords     = {PROSTATE-CANCER,EGFR MUTATIONS,FREQUENT MUTATION,NEUROENDOCRINE TUMORS,ACUTE LYMPHOBLASTIC-LEUKEMIA,MOUSE MODEL,P53 REGULATION,EPH-RECEPTOR,E-CADHERIN,GENE},
  language     = {eng},
  number       = {10},
  pages        = {1104--1110},
  title        = {Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer},
  url          = {http://dx.doi.org/10.1038/ng.2396},
  volume       = {44},
  year         = {2012},
}

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