Comprehensive genomic profiles of small cell lung cancer

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Fältnamn	Indikatorer	Metadata
000		06545naa a2201465 4500
001		oai:DiVA.org:uu-261237
003		SwePub
008		150831s2015 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2612372 URI
024	7	a https://doi.org/10.1038/nature146642 DOI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a George, Julie4 aut
245	1 0	a Comprehensive genomic profiles of small cell lung cancer
264		c 2015-07-13
264	1	b Springer Science and Business Media LLC,c 2015
338		a print2 rdacarrier
520		a 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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng
700	1	a Lim, Jing Shan4 aut
700	1	a Jang, Se Jin4 aut
700	1	a Cun, Yupeng4 aut
700	1	a Ozretic, Luka4 aut
700	1	a Kong, Gu4 aut
700	1	a Leenders, Frauke4 aut
700	1	a Lu, Xin4 aut
700	1	a Fernandez-Cuesta, Lynnette4 aut
700	1	a Bosco, Graziella4 aut
700	1	a Mueller, Christian4 aut
700	1	a Dahmen, Ilona4 aut
700	1	a Jahchan, Nadine S.4 aut
700	1	a Park, Kwon-Sik4 aut
700	1	a Yang, Dian4 aut
700	1	a Karnezis, Anthony N.4 aut
700	1	a Vaka, Dedeepya4 aut
700	1	a Torres, Angela4 aut
700	1	a Wang, Maia Segura4 aut
700	1	a Korbel, Jan O.4 aut
700	1	a Menon, Roopika4 aut
700	1	a Chun, Sung-Min4 aut
700	1	a Kim, Deokhoon4 aut
700	1	a Wilkerson, Matt4 aut
700	1	a Hayes, Neil4 aut
700	1	a Engelmann, David4 aut
700	1	a Puetzer, Brigitte4 aut
700	1	a Bos, Marc4 aut
700	1	a Michels, Sebastian4 aut
700	1	a Vlasic, Ignacija4 aut
700	1	a Seidel, Danila4 aut
700	1	a Pinther, Berit4 aut
700	1	a Schaub, Philipp4 aut
700	1	a Becker, Christian4 aut
700	1	a Altmueller, Janine4 aut
700	1	a Yokota, Jun4 aut
700	1	a Kohno, Takashi4 aut
700	1	a Iwakawa, Reika4 aut
700	1	a Tsuta, Koji4 aut
700	1	a Noguchi, Masayuki4 aut
700	1	a Muley, Thomas4 aut
700	1	a Hoffmann, Hans4 aut
700	1	a Schnabel, Philipp A.4 aut
700	1	a Petersen, Iver4 aut
700	1	a Chen, Yuan4 aut
700	1	a Soltermann, Alex4 aut
700	1	a Tischler, Verena4 aut
700	1	a Choi, Chang-min4 aut
700	1	a Kim, Yong-Hee4 aut
700	1	a Massion, Pierre P.4 aut
700	1	a Zou, Yong4 aut
700	1	a Jovanovic, Dragana4 aut
700	1	a Kontic, Milica4 aut
700	1	a Wright, Gavin M.4 aut
700	1	a Russell, Prudence A.4 aut
700	1	a Solomon, Benjamin4 aut
700	1	a Koch, Ina4 aut
700	1	a Lindner, Michael4 aut
700	1	a Muscarella, Lucia A.4 aut
700	1	a la Torre, Annamaria4 aut
700	1	a Field, John K.4 aut
700	1	a Jakopovic, Marko4 aut
700	1	a Knezevic, Jelena4 aut
700	1	a Castanos-Velez, Esmeralda4 aut
700	1	a Roz, Luca4 aut
700	1	a Pastorino, Ugo4 aut
700	1	a Brustugun, Odd-Terje4 aut
700	1	a Lund-Iversen, Marius4 aut
700	1	a Thunnissen, Erik4 aut
700	1	a Koehler, Jens4 aut
700	1	a Schuler, Martin4 aut
700	1	a Botling, Johanu Uppsala universitet,Institutionen för immunologi, genetik och patologi4 aut0 (Swepub:uu)johanbot
700	1	a Sandelin, Martinu Uppsala universitet,Lungmedicin och allergologi4 aut0 (Swepub:uu)masan425
700	1	a Sanchez-Cespedes, Montserrat4 aut
700	1	a Salvesen, Helga B.4 aut
700	1	a Achter, Viktor4 aut
700	1	a Lang, Ulrich4 aut
700	1	a Bogus, Magdalena4 aut
700	1	a Schneider, Peter M.4 aut
700	1	a Zander, Thomas4 aut
700	1	a Ansen, Sascha4 aut
700	1	a Hallek, Michael4 aut
700	1	a Wolf, Juergen4 aut
700	1	a Vingron, Martin4 aut
700	1	a Yatabe, Yasushi4 aut
700	1	a Travis, William D.4 aut
700	1	a Nuernberg, Peter4 aut
700	1	a Reinhardt, Christian4 aut
700	1	a Perner, Sven4 aut
700	1	a Heukamp, Lukas4 aut
700	1	a Buettner, Reinhard4 aut
700	1	a Haas, Stefan A.4 aut
700	1	a Brambilla, Elisabeth4 aut
700	1	a Peifer, Martin4 aut
700	1	a Sage, Julien4 aut
700	1	a Thomas, Roman K.4 aut
710	2	a Uppsala universitetb Institutionen för immunologi, genetik och patologi4 org
773	0	t Natured : Springer Science and Business Media LLCg 524:7563, s. 47-U73q 524:7563<47-U73x 0028-0836x 1476-4687
856	4	u https://pure.mpg.de/pubman/item/item_2261472_2/component/file_2273282/George.pdf
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-261237
856	4 8	u https://doi.org/10.1038/nature14664

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Av författaren/redakt...: George, Julie; Lim, Jing Shan; Jang, Se Jin; Cun, Yupeng; Ozretic, Luka; Kong, Gu; visa fler...; Leenders, Frauke; Lu, Xin; Fernandez-Cuesta ...; Bosco, Graziella; Mueller, Christi ...; Dahmen, Ilona; Jahchan, Nadine ...; Park, Kwon-Sik; Yang, Dian; Karnezis, Anthon ...; Vaka, Dedeepya; Torres, Angela; Wang, Maia Segur ...; Korbel, Jan O.; Menon, Roopika; Chun, Sung-Min; Kim, Deokhoon; Wilkerson, Matt; Hayes, Neil; Engelmann, David; Puetzer, Brigitt ...; Bos, Marc; Michels, Sebasti ...; Vlasic, Ignacija; Seidel, Danila; Pinther, Berit; Schaub, Philipp; Becker, Christia ...; Altmueller, Jani ...; Yokota, Jun; Kohno, Takashi; Iwakawa, Reika; Tsuta, Koji; Noguchi, Masayuk ...; Muley, Thomas; Hoffmann, Hans; Schnabel, Philip ...; Petersen, Iver; Chen, Yuan; Soltermann, Alex; Tischler, Verena; Choi, Chang-min; Kim, Yong-Hee; Massion, Pierre ...; Zou, Yong; Jovanovic, Draga ...; Kontic, Milica; Wright, Gavin M.; Russell, Prudenc ...; Solomon, Benjami ...; Koch, Ina; Lindner, Michael; Muscarella, Luci ...; la Torre, Annama ...; Field, John K.; Jakopovic, Marko; Knezevic, Jelena; Castanos-Velez, ...; Roz, Luca; Pastorino, Ugo; Brustugun, Odd-T ...; Lund-Iversen, Ma ...; Thunnissen, Erik; Koehler, Jens; Schuler, Martin; Botling, Johan; Sandelin, Martin; Sanchez-Cespedes ...; Salvesen, Helga ...; Achter, Viktor; Lang, Ulrich; Bogus, Magdalena; Schneider, Peter ...; Zander, Thomas; Ansen, Sascha; Hallek, Michael; Wolf, Juergen; Vingron, Martin; Yatabe, Yasushi; Travis, William ...; Nuernberg, Peter; Reinhardt, Chris ...; Perner, Sven; Heukamp, Lukas; Buettner, Reinha ...; Haas, Stefan A.; Brambilla, Elisa ...; Peifer, Martin; Sage, Julien; Thomas, Roman K.; visa färre...

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