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Comprehensive genom...
Comprehensive genomic profiles of small cell lung cancer
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George, Julie (author)
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Lim, Jing Shan (author)
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Jang, Se Jin (author)
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show more...
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Cun, Yupeng (author)
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Ozretic, Luka (author)
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Kong, Gu (author)
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Leenders, Frauke (author)
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Lu, Xin (author)
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Fernandez-Cuesta, Lynnette (author)
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Bosco, Graziella (author)
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Mueller, Christian (author)
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Dahmen, Ilona (author)
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Jahchan, Nadine S. (author)
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Park, Kwon-Sik (author)
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Yang, Dian (author)
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Karnezis, Anthony N. (author)
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Vaka, Dedeepya (author)
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Torres, Angela (author)
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Wang, Maia Segura (author)
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Korbel, Jan O. (author)
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Menon, Roopika (author)
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Chun, Sung-Min (author)
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Kim, Deokhoon (author)
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Wilkerson, Matt (author)
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Hayes, Neil (author)
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Engelmann, David (author)
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Puetzer, Brigitte (author)
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Bos, Marc (author)
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Michels, Sebastian (author)
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Vlasic, Ignacija (author)
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Seidel, Danila (author)
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Pinther, Berit (author)
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Schaub, Philipp (author)
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Becker, Christian (author)
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Altmueller, Janine (author)
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Yokota, Jun (author)
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Kohno, Takashi (author)
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Iwakawa, Reika (author)
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Tsuta, Koji (author)
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Noguchi, Masayuki (author)
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Muley, Thomas (author)
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Hoffmann, Hans (author)
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Schnabel, Philipp A. (author)
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Petersen, Iver (author)
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Chen, Yuan (author)
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Soltermann, Alex (author)
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Tischler, Verena (author)
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Choi, Chang-min (author)
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Kim, Yong-Hee (author)
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Massion, Pierre P. (author)
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Zou, Yong (author)
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Jovanovic, Dragana (author)
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Kontic, Milica (author)
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Wright, Gavin M. (author)
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Russell, Prudence A. (author)
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Solomon, Benjamin (author)
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Koch, Ina (author)
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Lindner, Michael (author)
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Muscarella, Lucia A. (author)
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la Torre, Annamaria (author)
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Field, John K. (author)
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Jakopovic, Marko (author)
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Knezevic, Jelena (author)
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Castanos-Velez, Esmeralda (author)
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Roz, Luca (author)
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Pastorino, Ugo (author)
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Brustugun, Odd-Terje (author)
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Lund-Iversen, Marius (author)
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Thunnissen, Erik (author)
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Koehler, Jens (author)
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Schuler, Martin (author)
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- Botling, Johan (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Sandelin, Martin (author)
- Uppsala universitet,Lungmedicin och allergologi
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Sanchez-Cespedes, Montserrat (author)
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Salvesen, Helga B. (author)
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Achter, Viktor (author)
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Lang, Ulrich (author)
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Bogus, Magdalena (author)
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Schneider, Peter M. (author)
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Zander, Thomas (author)
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Ansen, Sascha (author)
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Hallek, Michael (author)
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Wolf, Juergen (author)
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Vingron, Martin (author)
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Yatabe, Yasushi (author)
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Travis, William D. (author)
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Nuernberg, Peter (author)
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Reinhardt, Christian (author)
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Perner, Sven (author)
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Heukamp, Lukas (author)
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Buettner, Reinhard (author)
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Haas, Stefan A. (author)
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Brambilla, Elisabeth (author)
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Peifer, Martin (author)
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Sage, Julien (author)
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Thomas, Roman K. (author)
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(creator_code:org_t)
- 2015-07-13
- 2015
- English.
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
- Related links:
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https://pure.mpg.de/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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Nature
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To the university's database
- By the author/editor
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George, Julie
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Lim, Jing Shan
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Jang, Se Jin
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Cun, Yupeng
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Ozretic, Luka
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Kong, Gu
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show more...
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Leenders, Frauke
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Lu, Xin
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Fernandez-Cuesta ...
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Bosco, Graziella
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Mueller, Christi ...
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Dahmen, Ilona
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Jahchan, Nadine ...
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Park, Kwon-Sik
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Yang, Dian
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Karnezis, Anthon ...
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Vaka, Dedeepya
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Torres, Angela
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Wang, Maia Segur ...
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Korbel, Jan O.
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Menon, Roopika
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Chun, Sung-Min
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Kim, Deokhoon
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Wilkerson, Matt
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Hayes, Neil
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Engelmann, David
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Puetzer, Brigitt ...
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Bos, Marc
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Michels, Sebasti ...
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Vlasic, Ignacija
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Seidel, Danila
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Pinther, Berit
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Schaub, Philipp
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Becker, Christia ...
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Altmueller, Jani ...
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Yokota, Jun
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Kohno, Takashi
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Iwakawa, Reika
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Tsuta, Koji
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Noguchi, Masayuk ...
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Muley, Thomas
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Hoffmann, Hans
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Schnabel, Philip ...
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Petersen, Iver
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Chen, Yuan
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Soltermann, Alex
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Tischler, Verena
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Choi, Chang-min
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Kim, Yong-Hee
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Massion, Pierre ...
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Zou, Yong
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Jovanovic, Draga ...
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Kontic, Milica
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Wright, Gavin M.
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Russell, Prudenc ...
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Solomon, Benjami ...
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Koch, Ina
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Lindner, Michael
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Muscarella, Luci ...
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la Torre, Annama ...
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Field, John K.
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Jakopovic, Marko
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Knezevic, Jelena
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Castanos-Velez, ...
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Roz, Luca
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Pastorino, Ugo
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Brustugun, Odd-T ...
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Lund-Iversen, Ma ...
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Thunnissen, Erik
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Koehler, Jens
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Schuler, Martin
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Botling, Johan
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Sandelin, Martin
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Sanchez-Cespedes ...
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Salvesen, Helga ...
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Achter, Viktor
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Lang, Ulrich
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Bogus, Magdalena
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Schneider, Peter ...
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Zander, Thomas
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Ansen, Sascha
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Hallek, Michael
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Wolf, Juergen
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Vingron, Martin
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Yatabe, Yasushi
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Travis, William ...
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Nuernberg, Peter
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Reinhardt, Chris ...
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Perner, Sven
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Heukamp, Lukas
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Buettner, Reinha ...
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Haas, Stefan A.
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Brambilla, Elisa ...
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Peifer, Martin
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Sage, Julien
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Thomas, Roman K.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Nature
- By the university
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Uppsala University