Chan-Young Ock1, Bongjun Son2, Bhumsuk Keam3,4, Seung-Youn Lee2, Jaewoo Moon2, Hwanjong Kwak2, Sehui Kim5, Tae Min Kim1,6, Yoon Kyung Jeon5, Seong Keun Kwon6,7, J Hun Hah6,7, Se-Hoon Lee1,6, Tack-Kyun Kwon7, Dong-Wan Kim1,6, Hong-Gyun Wu8, Myung-Whun Sung6,7, Dae Seog Heo1,6. 1. Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea. 2. TheragenEtex Bio Institute, TheragenEtex, Suwon, Korea. 3. Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea. bhumsuk@snu.ac.kr. 4. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. bhumsuk@snu.ac.kr. 5. Department of Pathology, Seoul National University Hospital, Seoul, Korea. 6. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. 7. Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea. 8. Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea.
Abstract
PURPOSE: 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.
PURPOSE: 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.
Entities:
Keywords:
Concurrent chemoradiotherapy; Head and neck cancer; Induction chemotherapy; Survival; Targeted gene sequencing
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