An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors.
作者： D Chitale , Y Gong , B S Taylor , S Broderick , C Brennan
DOI: 10.1038/ONC.2009.135
关键词:
摘要: To address the biological heterogeneity of lung cancer, we studied 199 adenocarcinomas by integrating genome-wide data on copy number alterations and gene expression with full annotation for major known somatic mutations in this cancer. This showed non-random patterns significantly linked to EGFR KRAS mutation status distinct clinical outcomes, led discovery a striking association underexpression DUSP4, within broad region frequent single-copy loss 8p. DUSP4 is involved negative feedback control signaling, provide functional validation its role as growth suppressor EGFR-mutant adenocarcinoma. also associates p16/CDKN2A deletion defines subset cancer patients. Another novel observation that reciprocal relationship between LKB1 mutations. These results highlight power integrated genomics identify candidate driver genes recurrent regions alteration delineate oncogenetic pathways genetically complex common epithelial cancers.
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Seo Young Han, Sug Hyung Lee, Ro Ra Oh, Hong Sug Kim, Nam Jin Yoo, Won Sang Park, Su Young Kim, Jung Young Lee, Jik Young Park, Jong Heun Lee, Min Sun Shin, Hun Kyung Lee, Ji Youn Han, Ja June Jang, Alterations of the DR5/TRAIL Receptor 2 Gene in Non-Small Cell Lung Cancers Cancer Research. ,vol. 59, pp. 5683- 5686 ,(1999)
Helen Davies, Chris Hunter, Raffaella Smith, Philip Stephens, Chris Greenman, Graham Bignell, Jon Teague, Adam Butler, Sarah Edkins, Claire Stevens, Adrian Parker, Sarah O'Meara, Tim Avis, Syd Barthorpe, Lisa Brackenbury, Gemma Buck, Jody Clements, Jennifer Cole, Ed Dicks, Ken Edwards, Simon Forbes, Matthew Gorton, Kristian Gray, Kelly Halliday, Rachel Harrison, Katy Hills, Jonathon Hinton, David Jones, Vivienne Kosmidou, Ross Laman, Richard Lugg, Andrew Menzies, Janet Perry, Robert Petty, Keiran Raine, Rebecca Shepherd, Alexandra Small, Helen Solomon, Yvonne Stephens, Calli Tofts, Jennifer Varian, Anthony Webb, Sofie West, Sara Widaa, Andrew Yates, Francis Brasseur, Colin S Cooper, Adrienne M Flanagan, Anthony Green, Maggie Knowles, Suet Y Leung, Leendert HJ Looijenga, Bruce Malkowicz, Marco A Pierotti, Bin T Teh, Siu T Yuen, Sunil R Lakhani, Douglas F Easton, Barbara L Weber, Peter Goldstraw, Andrew G Nicholson, Richard Wooster, Michael R Stratton, P Andrew Futreal, None, Somatic Mutations of the Protein Kinase Gene Family in Human Lung Cancer Cancer Research. ,vol. 65, pp. 7591- 7595 ,(2005) , 10.1158/0008-5472.CAN-05-1855
Sreenath V. Sharma, Daphne W. Bell, Jeffrey Settleman, Daniel A. Haber, Epidermal growth factor receptor mutations in lung cancer Nature Reviews Cancer. ,vol. 7, pp. 169- 181 ,(2007) , 10.1038/NRC2088
Toru Furukawa, Makoto Sunamura, Fuyuhiko Motoi, Seiki Matsuno, Akira Horii, Potential Tumor Suppressive Pathway Involving DUSP6/MKP-3 in Pancreatic Cancer American Journal of Pathology. ,vol. 162, pp. 1807- 1815 ,(2003) , 10.1016/S0002-9440(10)64315-5
Scott W Lowe, Charles J Sherr, Tumor suppression by Ink4a-Arf: progress and puzzles Current Opinion in Genetics & Development. ,vol. 13, pp. 77- 83 ,(2003) , 10.1016/S0959-437X(02)00013-8
Jenifer L. Marks, Stephen Broderick, Qin Zhou, Dhananjay Chitale, Allan R. Li, Maureen F. Zakowski, Mark G. Kris, Valerie W. Rusch, Christopher G. Azzoli, Venkatraman E. Seshan, Marc Ladanyi, William Pao, Prognostic and Therapeutic Implications of EGFR and KRAS Mutations in Resected Lung Adenocarcinoma Journal of Thoracic Oncology. ,vol. 3, pp. 111- 116 ,(2008) , 10.1097/JTO.0B013E318160C607
Susumu Kobayashi, Takeshi Shimamura, Stefano Monti, Ulrich Steidl, Christopher J. Hetherington, April M. Lowell, Todd Golub, Matthew Meyerson, Daniel G. Tenen, Geoffrey I. Shapiro, Balázs Halmos, Transcriptional profiling identifies cyclin D1 as a critical downstream effector of mutant epidermal growth factor receptor signaling. Cancer Research. ,vol. 66, pp. 11389- 11398 ,(2006) , 10.1158/0008-5472.CAN-06-2318
Gregory J. Riely, Mark G. Kris, Daniel Rosenbaum, Jenifer Marks, Allan Li, Dhananjay A. Chitale, Khedoudja Nafa, Elyn R. Riedel, Meier Hsu, William Pao, Vincent A. Miller, Marc Ladanyi, Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clinical Cancer Research. ,vol. 14, pp. 5731- 5734 ,(2008) , 10.1158/1078-0432.CCR-08-0646
, Comprehensive genomic characterization defines human glioblastoma genes and core pathways Nature. ,vol. 455, pp. 1061- 1068 ,(2008) , 10.1038/NATURE07385
Jenifer L. Marks, Michael D. McLellan, Maureen F. Zakowski, Alex E. Lash, Yumi Kasai, Stephen Broderick, Inderpal S. Sarkaria, DuyKhanh Pham, Bhuvanesh Singh, Tracie L. Miner, Ginger A. Fewell, Lucinda L. Fulton, Elaine R. Mardis, Richard K. Wilson, Mark G. Kris, Valerie W. Rusch, Harold Varmus, William Pao, Mutational Analysis of EGFR and Related Signaling Pathway Genes in Lung Adenocarcinomas Identifies a Novel Somatic Kinase Domain Mutation in FGFR4 PLOS ONE. ,vol. 2, ,(2007) , 10.1371/JOURNAL.PONE.0000426