title: Integrative and comparative genomic analysis of lung squamous cell carcinomas in East Asian patients.
abstract: OBJECTIVE
  Lung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients.
  
  
  METHODS
  We performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.
  
  
  RESULTS
  This cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC.
  
  
  CONCLUSIONS
  These findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.
authors: Youngwook Kim, Ji-ae Yoon, Yoomi Lee, Yeong Kyung Yoo, and Keunchil Park, Samsung Medical Center, Samsung Biomedical Research Institute; Jong-Mu Sun, Hong Kwan Kim, Yong Soo Choi, Kwhanmien Kim, Young Mog Shim, Yoon-La Choi, Jhingook Kim, Jin Seok Ahn, Myung-Ju Ahn, and Keunchil Park, Samsung Medical Center, Sungkyunkwan University School of Medicine; Sukki Cho, Seoul National University Bundang Hospital, College of Medicine, Seoul National University, Seoul; In-Jae Oh, Kyu-Sik Kim, Sang-Yun Song, Kook-Ju Na, and Young-Chul Kim, Chonnam National University Hwasun Hospital, Jeonnam, Republic of Korea; Peter S. Hammerman, Jaegil Kim, Chandra Sekhar Pedamallu, Kristian Cibulskis, Michael S. Lawrence, Petar Stojanov, Scott L. Carter, Aaron McKenna, Chip Stewart, Andrey Y. Sivachenko, Gad Getz, and Matthew Meyerson, Broad Institute of Harvard and MIT, Cambridge; Matthew Meyerson, Harvard Medical School; Peter S. Hammerman and Chandra Sekhar Pedamallu, Dana-Farber Cancer Institute; Gad Getz, Massachusetts General Hospital Cancer Center, Boston, MA; and Matthew D. Wilkerson and D. Neil Hayes, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors: Youngwook
authors: Y
authors: Kim
authors: Peter S
authors: PS
authors: Hammerman
authors: Jaegil
authors: J
authors: Kim
authors: Ji-ae
authors: JA
authors: Yoon
authors: Yoomi
authors: Y
authors: Lee
authors: Jong-Mu
authors: JM
authors: Sun
authors: Matthew D
authors: MD
authors: Wilkerson
authors: Chandra Sekhar
authors: CS
authors: Pedamallu
authors: Kristian
authors: K
authors: Cibulskis
authors: Yeong Kyung
authors: YK
authors: Yoo
authors: Michael S
authors: MS
authors: Lawrence
authors: Petar
authors: P
authors: Stojanov
authors: Scott L
authors: SL
authors: Carter
authors: Aaron
authors: A
authors: McKenna
authors: Chip
authors: C
authors: Stewart
authors: Andrey Y
authors: AY
authors: Sivachenko
authors: In-Jae
authors: IJ
authors: Oh
authors: Hong Kwan
authors: HK
authors: Kim
authors: Yong Soo
authors: YS
authors: Choi
authors: Kwhanmien
authors: K
authors: Kim
authors: Young Mog
authors: YM
authors: Shim
authors: Kyu-Sik
authors: KS
authors: Kim
authors: Sang-Yun
authors: SY
authors: Song
authors: Kook-Joo
authors: KJ
authors: Na
authors: Yoon-La
authors: YL
authors: Choi
authors: D Neil
authors: DN
authors: Hayes
authors: Jhingook
authors: J
authors: Kim
authors: Sukki
authors: S
authors: Cho
authors: Young-Chul
authors: YC
authors: Kim
authors: Jin Seok
authors: JS
authors: Ahn
authors: Myung-Ju
authors: MJ
authors: Ahn
authors: Gad
authors: G
authors: Getz
authors: Matthew
authors: M
authors: Meyerson
authors: Keunchil
authors: K
authors: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000072019:Kelch-Like ECH-Associated Protein 1; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D056910:Republic of Korea; D016160:Retinoblastoma Protein / Q000235:genetics; D012907:Smoking; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014481:United States; D044465:White People / Q000235:genetics
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C431364:KEAP1 protein, human; C120898:KMT2D protein, human; C495635:NFE2L2 protein, human; C495901:TP53 protein, human; C484760:PIK3CA protein, human