title: Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas.
abstract: To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined the exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor-normal pairs. Recurrent alterations in lung SqCCs were more similar to those of other squamous carcinomas than to alterations in lung ADCs. New significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types. New amplification peaks encompassed MIR21 in lung ADC, MIR205 in lung SqCC, and MAPK1 in both. Lung ADCs lacking receptor tyrosine kinase-Ras-Raf pathway alterations had mutations in SOS1, VAV1, RASA1, and ARHGAP35. Regarding neoantigens, 47% of the lung ADC and 53% of the lung SqCC tumors had at least five predicted neoepitopes. Although targeted therapies for lung ADC and SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes.
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Joshua D
authors.identifier: 0000-0003-0780-8662
authors.initials: JD
authors.lastname: Campbell
authors.affiliation: Department of Pathology and Immunology, Washington University, St. Louis, Missouri, USA.|Computer Technologies Laboratory, ITMO University, St. Petersburg, Russia.
authors.forename: Anton
authors.identifier: 0000-0002-0970-9353
authors.initials: A
authors.lastname: Alexandrov
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Jaegil
authors.initials: J
authors.lastname: Kim
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Wala
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Alice H
authors.initials: AH
authors.lastname: Berger
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Chandra Sekhar
authors.identifier: 0000-0002-6704-058X
authors.initials: CS
authors.lastname: Pedamallu
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Sachet A
authors.initials: SA
authors.lastname: Shukla
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Guangwu
authors.initials: G
authors.lastname: Guo
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Angela N
authors.initials: AN
authors.lastname: Brooks
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Murray
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
authors.forename: Marcin
authors.initials: M
authors.lastname: Imielinski
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Ling
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Rehan
authors.initials: R
authors.lastname: Akbani
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Mara
authors.initials: M
authors.lastname: Rosenberg
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Cibulskis
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Aruna
authors.initials: A
authors.lastname: Ramachandran
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Collisson
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kwiatkowski
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lawrence
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Weinstein
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Roel G W
authors.initials: RG
authors.lastname: Verhaak
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Wu
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Hammerman
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cherniack
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.affiliation: Department of Pathology and Immunology, Washington University, St. Louis, Missouri, USA.
authors.forename: Maxim N
authors.initials: MN
authors.lastname: Artyomov
authors.affiliation: Department of Pathology and Immunology, Washington University, St. Louis, Missouri, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Schreiber
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
authors.affiliation: Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Matthew
authors.identifier: 0000-0002-9133-8108
authors.initials: M
authors.lastname: Meyerson
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000951:Antigens, Neoplasm; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D056915:DNA Copy Number Variations; D015894:Genome, Human; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D012008:Recurrence
chemical_list: D000951:Antigens, Neoplasm