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  Comprehensive genomic profiles of small cell lung cancer

George, J., Lim, J. S., Jang, S. J., Cun, Y., Ozretic, L., Kong, G., et al. (2015). Comprehensive genomic profiles of small cell lung cancer. Nature, 524(7563), 47-53. doi:10.1038/nature14664.

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© 2015 Macmillan Publishers Limited
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George, J., Author
Lim, J. S., Author
Jang, S. J., Author
Cun, Y., Author
Ozretic, L., Author
Kong, G., Author
Leenders, F., Author
Lu, X., Author
Fernandez-Cuesta, L., Author
Bosco, G., Author
Müller, C., Author
Dahmen, I., Author
Jahchan, N. S., Author
Park, K. S., Author
Yang, D., Author
Karnezis, A. N., Author
Vaka, D., Author
Torres, A., Author
Wang, M. S., Author
Korbel, J. O., Author
Menon, R., AuthorChun, S. M., AuthorKim, D., AuthorWilkerson, M., AuthorHayes, N., AuthorEngelmann, D., AuthorPutzer, B., AuthorBos, M., AuthorMichels, S., AuthorVlasic, I., AuthorSeidel, D., AuthorPinther, B., AuthorSchaub, P., AuthorBecker, C., AuthorAltmuller, J., AuthorYokota, J., AuthorKohno, T., AuthorIwakawa, R., AuthorTsuta, K., AuthorNoguchi, M., AuthorMuley, T., AuthorHoffmann, H., AuthorSchnabel, P. A., AuthorPetersen, I., AuthorChen, Y., AuthorSoltermann, A., AuthorTischler, V., AuthorChoi, C. M., AuthorKim, Y. H., AuthorMassion, P. P., AuthorZou, Y., AuthorJovanovic, D., AuthorKontic, M., AuthorWright, G. M., AuthorRussell, P. A., AuthorSolomon, B., AuthorKoch, I., AuthorLindner, M., AuthorMuscarella, L. A., Authorla Torre, A., AuthorField, J. K., AuthorJakopovic, M., AuthorKnezevic, J., AuthorCastanos-Velez, E., AuthorRoz, L., AuthorPastorino, U., AuthorBrustugun, O. T., AuthorLund-Iversen, M., AuthorThunnissen, E., AuthorKöhler, J., AuthorSchuler, M., AuthorBotling, J., AuthorSandelin, M., AuthorSanchez-Cespedes, M., AuthorSalvesen, H. B., AuthorAchter, V., AuthorLang, U., AuthorBogus, M., AuthorSchneider, P. M., AuthorZander, T., AuthorAnsen, S., AuthorHallek, M., AuthorWolf, J., AuthorVingron, M.1, Author              Yatabe, Y., AuthorTravis, W. D., AuthorNurnberg, P., AuthorReinhardt, C., AuthorPerner, S., AuthorHeukamp, L., AuthorBüttner, R., AuthorHaas, S. A.2, Author              Brambilla, E., AuthorPeifer, M., AuthorSage, J., AuthorThomas, R. K., Author more..
Affiliations:
1Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              
2Gene Structure and Array Design (Stefan Haas), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479640              

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 Abstract: We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Deltaex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.

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Language(s): eng - English
 Dates: 2015-07-132015-08-06
 Publication Status: Published in print
 Pages: 7
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/nature14664
ISSN: 1476-4687 (Electronic)0028-0836 (Print)
 Degree: -

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Title: Nature
  Abbreviation : Nature
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 524 (7563) Sequence Number: - Start / End Page: 47 - 53 Identifier: ISSN: 0028-0836
CoNE: https://pure.mpg.de/cone/journals/resource/954925427238