title: Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing.
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.
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Marcin
authors.initials: M
authors.lastname: Imielinski
authors.forename: Alice H
authors.initials: AH
authors.lastname: Berger
authors.forename: Peter S
authors.initials: PS
authors.lastname: Hammerman
authors.forename: Bryan
authors.initials: B
authors.lastname: Hernandez
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Pugh
authors.forename: Eran
authors.initials: E
authors.lastname: Hodis
authors.forename: Jeonghee
authors.initials: J
authors.lastname: Cho
authors.forename: James
authors.initials: J
authors.lastname: Suh
authors.forename: Marzia
authors.initials: M
authors.lastname: Capelletti
authors.forename: Andrey
authors.initials: A
authors.lastname: Sivachenko
authors.forename: Carrie
authors.initials: C
authors.lastname: Sougnez
authors.forename: Daniel
authors.initials: D
authors.lastname: Auclair
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lawrence
authors.forename: Petar
authors.initials: P
authors.lastname: Stojanov
authors.forename: Kristian
authors.initials: K
authors.lastname: Cibulskis
authors.forename: Kyusam
authors.initials: K
authors.lastname: Choi
authors.forename: Luc
authors.initials: L
authors.lastname: de Waal
authors.forename: Tanaz
authors.initials: T
authors.lastname: Sharifnia
authors.forename: Angela
authors.initials: A
authors.lastname: Brooks
authors.forename: Heidi
authors.initials: H
authors.lastname: Greulich
authors.forename: Shantanu
authors.initials: S
authors.lastname: Banerji
authors.forename: Thomas
authors.initials: T
authors.lastname: Zander
authors.forename: Danila
authors.initials: D
authors.lastname: Seidel
authors.forename: Frauke
authors.initials: F
authors.lastname: Leenders
authors.forename: Sascha
authors.initials: S
authors.lastname: Ansén
authors.forename: Corinna
authors.initials: C
authors.lastname: Ludwig
authors.forename: Walburga
authors.initials: W
authors.lastname: Engel-Riedel
authors.forename: Erich
authors.initials: E
authors.lastname: Stoelben
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wolf
authors.forename: Chandra
authors.initials: C
authors.lastname: Goparju
authors.forename: Kristin
authors.initials: K
authors.lastname: Thompson
authors.forename: Wendy
authors.initials: W
authors.lastname: Winckler
authors.forename: David
authors.initials: D
authors.lastname: Kwiatkowski
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: William
authors.initials: W
authors.lastname: Pao
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.forename: Harvey I
authors.initials: HI
authors.lastname: Pass
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Gabriel
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Roman K
authors.initials: RK
authors.lastname: Thomas
authors.forename: Levi A
authors.initials: LA
authors.lastname: Garraway
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D059472:Exome; D005260:Female; D052138:Genes, Neoplasm; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate