TY  - JOUR
AU  - George, Julie
AU  - Lim, Jing Shan
AU  - Jang, Se Jin
AU  - Cun, Yupeng
AU  - Ozretic, Luka
AU  - Kong, Gu
AU  - Leenders, Frauke
AU  - Lu, Xin
AU  - Fernandez-Cuesta, Lynnette
AU  - Bosco, Graziella
AU  - Mueller, Christian
AU  - Dahmen, Ilona
AU  - Jahchan, Nadine S.
AU  - Park, Kwon-Sik
AU  - Yang, Dian
AU  - Karnezis, Anthony N.
AU  - Vaka, Dedeepya
AU  - Torres, Angela
AU  - Wang, Maia Segura
AU  - Korbel, Jan O.
AU  - Menon, Roopika
AU  - Chun, Sung-Min
AU  - Kim, Deokhoon
AU  - Wilkerson, Matt
AU  - Hayes, Neil
AU  - Engelmann, David
AU  - Puetzer, Brigitte
AU  - Bos, Marc
AU  - Michels, Sebastian
AU  - Vlasic, Ignacija
AU  - Seidel, Danila
AU  - Pinther, Berit
AU  - Schaub, Philipp
AU  - Becker, Christian
AU  - Altmueller, Janine
AU  - Yokota, Jun
AU  - Kohno, Takashi
AU  - Iwakawa, Reika
AU  - Tsuta, Koji
AU  - Noguchi, Masayuki
AU  - Muley, Thomas
AU  - Hoffmann, Hans
AU  - Schnabel, Philipp A.
AU  - Petersen, Iver
AU  - Chen, Yuan
AU  - Soltermann, Alex
AU  - Tischler, Verena
AU  - Choi, Chang-min
AU  - Kim, Yong-Hee
AU  - Massion, Pierre P.
AU  - Zou, Yong
AU  - Jovanovic, Dragana
AU  - Kontic, Milica
AU  - Wright, Gavin M.
AU  - Russell, Prudence A.
AU  - Solomon, Benjamin
AU  - Koch, Ina
AU  - Lindner, Michael
AU  - Muscarella, Lucia A.
AU  - la Torre, Annamaria
AU  - Field, John K.
AU  - Jakopovic, Marko
AU  - Knežević, Jelena
AU  - Castanos-Velez, Esmeralda
AU  - Roz, Luca
AU  - Pastorino, Ugo
AU  - Brustugun, Odd-Terje
AU  - Lund-Iversen, Marius
AU  - Thunnissen, Erik
AU  - Koehler, Jens
AU  - Schuler, Martin
AU  - Botling, Johan
AU  - Sandelin, Martin
AU  - Sanchez-Cespedes, Montserrat
AU  - Salvesen, Helga B.
AU  - Achter, Viktor
AU  - Lang, Ulrich
AU  - Bogus, Magdalena
AU  - Schneider, Peter M.
AU  - Zander, Thomas
AU  - Ansen, Sascha
AU  - Hallek, Michael
AU  - Wolf, Juergen
AU  - Vingron, Martin
AU  - Yatabe, Yasushi
AU  - Travis, William D.
AU  - Nuernberg, Peter
AU  - Reinhardt, Christian
AU  - Perner, Sven
AU  - Heukamp, Lukas
AU  - Buettner, Reinhard
AU  - Haas, Stefan A.
AU  - Brambilla, Elisabeth
AU  - Peifer, Martin
AU  - Sage, Julien
AU  - Thomas, Roman K.
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/685
AB  - 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, TP73Dex2/3. 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.
T2  - Nature
T1  - Comprehensive genomic profiles of small cell lung cancer
VL  - 524
IS  - 7563
SP  - 47
EP  - 53
DO  - 10.1038/nature14664
ER  - 

@article{
author = "George, Julie and Lim, Jing Shan and Jang, Se Jin and Cun, Yupeng and Ozretic, Luka and Kong, Gu and Leenders, Frauke and Lu, Xin and Fernandez-Cuesta, Lynnette and Bosco, Graziella and Mueller, Christian and Dahmen, Ilona and Jahchan, Nadine S. and Park, Kwon-Sik and Yang, Dian and Karnezis, Anthony N. and Vaka, Dedeepya and Torres, Angela and Wang, Maia Segura and Korbel, Jan O. and Menon, Roopika and Chun, Sung-Min and Kim, Deokhoon and Wilkerson, Matt and Hayes, Neil and Engelmann, David and Puetzer, Brigitte and Bos, Marc and Michels, Sebastian and Vlasic, Ignacija and Seidel, Danila and Pinther, Berit and Schaub, Philipp and Becker, Christian and Altmueller, Janine and Yokota, Jun and Kohno, Takashi and Iwakawa, Reika and Tsuta, Koji and Noguchi, Masayuki and Muley, Thomas and Hoffmann, Hans and Schnabel, Philipp A. and Petersen, Iver and Chen, Yuan and Soltermann, Alex and Tischler, Verena and Choi, Chang-min and Kim, Yong-Hee and Massion, Pierre P. and Zou, Yong and Jovanovic, Dragana and Kontic, Milica and Wright, Gavin M. and Russell, Prudence A. and Solomon, Benjamin and Koch, Ina and Lindner, Michael and Muscarella, Lucia A. and la Torre, Annamaria and Field, John K. and Jakopovic, Marko and Knežević, Jelena and Castanos-Velez, Esmeralda and Roz, Luca and Pastorino, Ugo and Brustugun, Odd-Terje and Lund-Iversen, Marius and Thunnissen, Erik and Koehler, Jens and Schuler, Martin and Botling, Johan and Sandelin, Martin and Sanchez-Cespedes, Montserrat and Salvesen, Helga B. and Achter, Viktor and Lang, Ulrich and Bogus, Magdalena and Schneider, Peter M. and Zander, Thomas and Ansen, Sascha and Hallek, Michael and Wolf, Juergen and Vingron, Martin and Yatabe, Yasushi and Travis, William D. and Nuernberg, Peter and Reinhardt, Christian and Perner, Sven and Heukamp, Lukas and Buettner, Reinhard and Haas, Stefan A. and Brambilla, Elisabeth and Peifer, Martin and Sage, Julien and Thomas, Roman K.",
year = "2015",
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, TP73Dex2/3. 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.",
journal = "Nature",
title = "Comprehensive genomic profiles of small cell lung cancer",
volume = "524",
number = "7563",
pages = "47-53",
doi = "10.1038/nature14664"
}

George, J., Lim, J. S., Jang, S. J., Cun, Y., Ozretic, L., Kong, G., Leenders, F., Lu, X., Fernandez-Cuesta, L., Bosco, G., Mueller, C., Dahmen, I., Jahchan, N. S., Park, K., Yang, D., Karnezis, A. N., Vaka, D., Torres, A., Wang, M. S., Korbel, J. O., Menon, R., Chun, S., Kim, D., Wilkerson, M., Hayes, N., Engelmann, D., Puetzer, B., Bos, M., Michels, S., Vlasic, I., Seidel, D., Pinther, B., Schaub, P., Becker, C., Altmueller, J., Yokota, J., Kohno, T., Iwakawa, R., Tsuta, K., Noguchi, M., Muley, T., Hoffmann, H., Schnabel, P. A., Petersen, I., Chen, Y., Soltermann, A., Tischler, V., Choi, C., Kim, Y., Massion, P. P., Zou, Y., Jovanovic, D., Kontic, M., Wright, G. M., Russell, P. A., Solomon, B., Koch, I., Lindner, M., Muscarella, L. A., la Torre, A., Field, J. K., Jakopovic, M., Knežević, J., Castanos-Velez, E., Roz, L., Pastorino, U., Brustugun, O., Lund-Iversen, M., Thunnissen, E., Koehler, J., Schuler, M., Botling, J., Sandelin, M., Sanchez-Cespedes, M., Salvesen, H. B., Achter, V., Lang, U., Bogus, M., Schneider, P. M., Zander, T., Ansen, S., Hallek, M., Wolf, J., Vingron, M., Yatabe, Y., Travis, W. D., Nuernberg, P., Reinhardt, C., Perner, S., Heukamp, L., Buettner, R., Haas, S. A., Brambilla, E., Peifer, M., Sage, J.,& Thomas, R. K.. (2015). Comprehensive genomic profiles of small cell lung cancer. in Nature, 524(7563), 47-53.
https://doi.org/10.1038/nature14664

George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, Leenders F, Lu X, Fernandez-Cuesta L, Bosco G, Mueller C, Dahmen I, Jahchan NS, Park K, Yang D, Karnezis AN, Vaka D, Torres A, Wang MS, Korbel JO, Menon R, Chun S, Kim D, Wilkerson M, Hayes N, Engelmann D, Puetzer B, Bos M, Michels S, Vlasic I, Seidel D, Pinther B, Schaub P, Becker C, Altmueller J, Yokota J, Kohno T, Iwakawa R, Tsuta K, Noguchi M, Muley T, Hoffmann H, Schnabel PA, Petersen I, Chen Y, Soltermann A, Tischler V, Choi C, Kim Y, Massion PP, Zou Y, Jovanovic D, Kontic M, Wright GM, Russell PA, Solomon B, Koch I, Lindner M, Muscarella LA, la Torre A, Field JK, Jakopovic M, Knežević J, Castanos-Velez E, Roz L, Pastorino U, Brustugun O, Lund-Iversen M, Thunnissen E, Koehler J, Schuler M, Botling J, Sandelin M, Sanchez-Cespedes M, Salvesen HB, Achter V, Lang U, Bogus M, Schneider PM, Zander T, Ansen S, Hallek M, Wolf J, Vingron M, Yatabe Y, Travis WD, Nuernberg P, Reinhardt C, Perner S, Heukamp L, Buettner R, Haas SA, Brambilla E, Peifer M, Sage J, Thomas RK. Comprehensive genomic profiles of small cell lung cancer. in Nature. 2015;524(7563):47-53.
doi:10.1038/nature14664 .

George, Julie, Lim, Jing Shan, Jang, Se Jin, Cun, Yupeng, Ozretic, Luka, Kong, Gu, Leenders, Frauke, Lu, Xin, Fernandez-Cuesta, Lynnette, Bosco, Graziella, Mueller, Christian, Dahmen, Ilona, Jahchan, Nadine S., Park, Kwon-Sik, Yang, Dian, Karnezis, Anthony N., Vaka, Dedeepya, Torres, Angela, Wang, Maia Segura, Korbel, Jan O., Menon, Roopika, Chun, Sung-Min, Kim, Deokhoon, Wilkerson, Matt, Hayes, Neil, Engelmann, David, Puetzer, Brigitte, Bos, Marc, Michels, Sebastian, Vlasic, Ignacija, Seidel, Danila, Pinther, Berit, Schaub, Philipp, Becker, Christian, Altmueller, Janine, Yokota, Jun, Kohno, Takashi, Iwakawa, Reika, Tsuta, Koji, Noguchi, Masayuki, Muley, Thomas, Hoffmann, Hans, Schnabel, Philipp A., Petersen, Iver, Chen, Yuan, Soltermann, Alex, Tischler, Verena, Choi, Chang-min, Kim, Yong-Hee, Massion, Pierre P., Zou, Yong, Jovanovic, Dragana, Kontic, Milica, Wright, Gavin M., Russell, Prudence A., Solomon, Benjamin, Koch, Ina, Lindner, Michael, Muscarella, Lucia A., la Torre, Annamaria, Field, John K., Jakopovic, Marko, Knežević, Jelena, Castanos-Velez, Esmeralda, Roz, Luca, Pastorino, Ugo, Brustugun, Odd-Terje, Lund-Iversen, Marius, Thunnissen, Erik, Koehler, Jens, Schuler, Martin, Botling, Johan, Sandelin, Martin, Sanchez-Cespedes, Montserrat, Salvesen, Helga B., Achter, Viktor, Lang, Ulrich, Bogus, Magdalena, Schneider, Peter M., Zander, Thomas, Ansen, Sascha, Hallek, Michael, Wolf, Juergen, Vingron, Martin, Yatabe, Yasushi, Travis, William D., Nuernberg, Peter, Reinhardt, Christian, Perner, Sven, Heukamp, Lukas, Buettner, Reinhard, Haas, Stefan A., Brambilla, Elisabeth, Peifer, Martin, Sage, Julien, Thomas, Roman K., "Comprehensive genomic profiles of small cell lung cancer" in Nature, 524, no. 7563 (2015):47-53,
https://doi.org/10.1038/nature14664 . .