title: Identification of genomic mutations associated with clinical outcomes of induction chemotherapy in patients with head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  We performed deep sequencing of target genes in head and neck squamous cell carcinoma (HNSCC) tumors to identify somatic mutations that are associated with induction chemotherapy (IC) response.
  
  
  METHODS
  Patients who were diagnosed with HNSCC were retrospectively identified. Patients who were treated with IC were divided into two groups: good responders and poor responders by tumor response and progression-free survival. Targeted gene sequencing for 2404 somatic mutations of 44 genes was performed on HNSCC tissues. Mutations with total coverage of <500 were excluded, and the cutoff for altered allele frequency was >10 %.
  
  
  RESULTS
  Of the 71 patients, 45 were treated upfront with IC. Mean total coverage was 1941 per locus, and 42.2 % of tumors had TP53 mutations. Thirty-three mutations in TP53, NOTCH3, FGFR2, FGFR3, ATM, EGFR, MET, PTEN, FBXW7, SYNE1, and SUFU were frequently altered in poor responders. Among the patients who were treated with IC, those with unfavorable genomic profiles had significantly poorer overall survival than those without unfavorable genomic profiles (hazard ratio 6.45, 95 % confidence interval 2.07-20.10, P < 0.001).
  
  
  CONCLUSIONS
  Comprehensive analysis of mutation frequencies identified unfavorable genomic profiles, and the patients without unfavorable genomic profiles can obtain clinical benefits from IC in patients with HNSCC.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
authors.forename: Chan-Young
authors.initials: CY
authors.lastname: Ock
authors.affiliation: TheragenEtex Bio Institute, TheragenEtex, Suwon, Korea.
authors.forename: Bongjun
authors.initials: B
authors.lastname: Son
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea. bhumsuk@snu.ac.kr.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. bhumsuk@snu.ac.kr.
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.affiliation: TheragenEtex Bio Institute, TheragenEtex, Suwon, Korea.
authors.forename: Seung-Youn
authors.initials: SY
authors.lastname: Lee
authors.affiliation: TheragenEtex Bio Institute, TheragenEtex, Suwon, Korea.
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Moon
authors.affiliation: TheragenEtex Bio Institute, TheragenEtex, Suwon, Korea.
authors.forename: Hwanjong
authors.initials: H
authors.lastname: Kwak
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sehui
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Seong Keun
authors.initials: SK
authors.lastname: Kwon
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: J Hun
authors.initials: JH
authors.lastname: Hah
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Tack-Kyun
authors.initials: TK
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hong-Gyun
authors.initials: HG
authors.lastname: Wu
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Myung-Whun
authors.initials: MW
authors.lastname: Sung
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy; D058534:Class I Phosphatidylinositol 3-Kinases; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
keywords: Concurrent chemoradiotherapy; Head and neck cancer; Induction chemotherapy; Survival; Targeted gene sequencing