Imielinski, Marcin, Berger, Alice H., Hammerman, Peter S., Hernandez, Bryan, Pugh, Trevor J., Hodis, Eran, Cho, Jeonghee, Suh, James, Capelletti, Marzia ORCID: 0000-0001-5095-7060, Sivachenko, Andrey, Sougnez, Carrie, Auclair, Daniel, Lawrence, Michael S., Stojanov, Petar, Cibulskis, Kristian, Choi, Kyusam, de Waal, Luc, Sharifnia, Tanaz, Brooks, Angela, Greulich, Heidi, Banerji, Shantanu, Zander, Thomas, Seidel, Danila ORCID: 0000-0003-4388-3117, Leenders, Frauke, Ansen, Sascha, Ludwig, Corinna, Engel-Riedel, Walburga, Stoelben, Erich, Wolf, Juergen, Goparju, Chandra, Thompson, Kristin, Winckler, Wendy, Kwiatkowski, David, Johnson, Bruce E., Jaenne, Pasi A., Miller, Vincent A., Pao, William, Travis, William D., Pass, Harvey I., Gabriel, Stacey B., Lander, Eric S., Thomas, Roman K., Garraway, Levi A., Getz, Gad and Meyerson, Matthew ORCID: 0000-0002-9133-8108 (2012). Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing. Cell, 150 (6). S. 1107 - 1121. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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Abstract

Lung adenocarcinoma, the most common subtype of non-small cell lung cancer, is responsible for more than 500,000 deaths per year worldwide. Here, we report exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs. These analyses revealed a mean exonic somatic mutation rate of 12.0 events/megabase and identified the majority of genes previously reported as significantly mutated in lung adenocarcinoma. In addition, we identified statistically recurrent somatic mutations in the splicing factor gene U2AF1 and truncating mutations affecting RBM10 and ARID1A. Analysis of nucleotide context-specific mutation signatures grouped the sample set into distinct clusters that correlated with smoking history and alterations of reported lung adenocarcinoma genes. Whole-genome sequence analysis revealed frequent structural rearrangements, including in-frame exonic alterations within EGFR and SIK2 kinases. The candidate genes identified in this study are attractive targets for biological characterization and therapeutic targeting of lung adenocarcinoma.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Imielinski, MarcinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berger, Alice H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hammerman, Peter S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hernandez, BryanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pugh, Trevor J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hodis, EranUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cho, JeongheeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suh, JamesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Capelletti, MarziaUNSPECIFIEDorcid.org/0000-0001-5095-7060UNSPECIFIED
Sivachenko, AndreyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sougnez, CarrieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Auclair, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lawrence, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stojanov, PetarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cibulskis, KristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Choi, KyusamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Waal, LucUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sharifnia, TanazUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brooks, AngelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greulich, HeidiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Banerji, ShantanuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seidel, DanilaUNSPECIFIEDorcid.org/0000-0003-4388-3117UNSPECIFIED
Leenders, FraukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ansen, SaschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ludwig, CorinnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engel-Riedel, WalburgaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoelben, ErichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goparju, ChandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thompson, KristinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winckler, WendyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kwiatkowski, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johnson, Bruce E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jaenne, Pasi A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miller, Vincent A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pao, WilliamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Travis, William D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pass, Harvey I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gabriel, Stacey B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lander, Eric S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, Roman K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garraway, Levi A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Getz, GadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meyerson, MatthewUNSPECIFIEDorcid.org/0000-0002-9133-8108UNSPECIFIED
URN: urn:nbn:de:hbz:38-483047
DOI: 10.1016/j.cell.2012.08.029
Journal or Publication Title: Cell
Volume: 150
Number: 6
Page Range: S. 1107 - 1121
Date: 2012
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4172
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GROWTH-FACTOR RECEPTOR; SOMATIC MUTATIONS; GENE-MUTATIONS; CANCER; GENOME; EGFR; LANDSCAPE; GEFITINIB; PATTERNS; REVEALSMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48304

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