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Somatic mutations affect key pathways in lung adenocarcinoma

Ding, Li (author)
Getz, Gad (author)
Wheeler, David A (author)
show more...
Mardis, Elaine R (author)
McLellan, Michael D (author)
Cibulskis, Kristian (author)
Sougnez, Carrie (author)
Greulich, Heidi (author)
Muzny, Donna M (author)
Morgan, Margaret B (author)
Fulton, Lucinda (author)
Fulton, Robert S (author)
Zhang, Qunyuan (author)
Wendl, Michael C (author)
Lawrence, Michael S (author)
Larson, David E (author)
Chen, Ken (author)
Dooling, David J (author)
Sabo, Aniko (author)
Hawes, Alicia C (author)
Shen, Hua (author)
Jhangiani, Shalini N (author)
Lewis, Lora R (author)
Hall, Otis (author)
Zhu, Yiming (author)
Mathew, Tittu (author)
Ren, Yanru (author)
Yao, Jiqiang (author)
Scherer, Steven E (author)
Clerc, Kerstin (author)
Metcalf, Ginger A (author)
Ng, Brian (author)
Milosavljevic, Aleksandar (author)
Gonzalez-Garay, Manuel L (author)
Osborne, John R (author)
Meyer, Rick (author)
Shi, Xiaoqi (author)
Tang, Yuzhu (author)
Koboldt, Daniel C (author)
Lin, Ling (author)
Abbott, Rachel (author)
Miner, Tracie L (author)
Pohl, Craig (author)
Fewell, Ginger (author)
Haipek, Carrie (author)
Schmidt, Heather (author)
Dunford-Shore, Brian H (author)
Kraja, Aldi (author)
Crosby, Seth D (author)
Sawyer, Christopher S (author)
Vickery, Tammi (author)
Sander, Sacha (author)
Robinson, Jody (author)
Winckler, Wendy (author)
Baldwin, Jennifer (author)
Chirieac, Lucian R (author)
Dutt, Amit (author)
Fennell, Tim (author)
Hanna, Megan (author)
Johnson, Bruce E (author)
Onofrio, Robert C (author)
Thomas, Roman K (author)
Tonon, Giovanni (author)
Weir, Barbara A (author)
Zhao, Xiaojun (author)
Ziaugra, Liuda (author)
Zody, Michael C. (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
Giordano, Thomas (author)
Orringer, Mark B (author)
Roth, Jack A (author)
Spitz, Margaret R (author)
Wistuba, Ignacio I (author)
Ozenberger, Bradley (author)
Good, Peter J (author)
Chang, Andrew C (author)
Beer, David G (author)
Watson, Mark A (author)
Ladanyi, Marc (author)
Broderick, Stephen (author)
Yoshizawa, Akihiko (author)
Travis, William D (author)
Pao, William (author)
Province, Michael A (author)
Weinstock, George M (author)
Varmus, Harold E (author)
Gabriel, Stacey B (author)
Lander, Eric S (author)
Gibbs, Richard A (author)
Meyerson, Matthew (author)
Wilson, Richard K (author)
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 (creator_code:org_t)
Springer Science and Business Media LLC, 2008
2008
English.
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.

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MEDICIN

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By the author/editor
Ding, Li
Getz, Gad
Wheeler, David A
Mardis, Elaine R
McLellan, Michae ...
Cibulskis, Krist ...
show more...
Sougnez, Carrie
Greulich, Heidi
Muzny, Donna M
Morgan, Margaret ...
Fulton, Lucinda
Fulton, Robert S
Zhang, Qunyuan
Wendl, Michael C
Lawrence, Michae ...
Larson, David E
Chen, Ken
Dooling, David J
Sabo, Aniko
Hawes, Alicia C
Shen, Hua
Jhangiani, Shali ...
Lewis, Lora R
Hall, Otis
Zhu, Yiming
Mathew, Tittu
Ren, Yanru
Yao, Jiqiang
Scherer, Steven ...
Clerc, Kerstin
Metcalf, Ginger ...
Ng, Brian
Milosavljevic, A ...
Gonzalez-Garay, ...
Osborne, John R
Meyer, Rick
Shi, Xiaoqi
Tang, Yuzhu
Koboldt, Daniel ...
Lin, Ling
Abbott, Rachel
Miner, Tracie L
Pohl, Craig
Fewell, Ginger
Haipek, Carrie
Schmidt, Heather
Dunford-Shore, B ...
Kraja, Aldi
Crosby, Seth D
Sawyer, Christop ...
Vickery, Tammi
Sander, Sacha
Robinson, Jody
Winckler, Wendy
Baldwin, Jennife ...
Chirieac, Lucian ...
Dutt, Amit
Fennell, Tim
Hanna, Megan
Johnson, Bruce E
Onofrio, Robert ...
Thomas, Roman K
Tonon, Giovanni
Weir, Barbara A
Zhao, Xiaojun
Ziaugra, Liuda
Zody, Michael C.
Giordano, Thomas
Orringer, Mark B
Roth, Jack A
Spitz, Margaret ...
Wistuba, Ignacio ...
Ozenberger, Brad ...
Good, Peter J
Chang, Andrew C
Beer, David G
Watson, Mark A
Ladanyi, Marc
Broderick, Steph ...
Yoshizawa, Akihi ...
Travis, William ...
Pao, William
Province, Michae ...
Weinstock, Georg ...
Varmus, Harold E
Gabriel, Stacey ...
Lander, Eric S
Gibbs, Richard A
Meyerson, Matthe ...
Wilson, Richard ...
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Nature
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Uppsala University

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