J Cancer Res Clin Oncol. 2016;142(4):873-83.
Identification of genomic mutations associated with clinical outcomes of induction chemotherapy in patients with head and neck squamous cell carcinoma.
제1저자 옥찬영 · 교신저자 김범석
소속 (8)
- Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
- TheragenEtex Bio Institute, TheragenEtex, Suwon, Korea.
- 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.
- Department of Pathology, Seoul National University Hospital, Seoul, Korea.
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
- Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea.
- 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.
Keywords
Concurrent chemoradiotherapyHead and neck cancerInduction chemotherapySurvivalTargeted gene sequencing
Conflict of interest statement
The authors declare that they have no competing interests.
그 밖의 정보
- 출판 형태
- Journal Article, Research Support, Non-U.S. Gov't
- 저널
- Journal of cancer research and clinical oncology · eISSN 1432-1335
- 전자 출판
- 2015-12-16
- MeSH
- Adult · Aged · Aged, 80 and over · Antineoplastic Combined Chemotherapy Protocols / therapeutic use · Carcinoma, Squamous Cell / genetics / mortality / therapy · Chemoradiotherapy · Class I Phosphatidylinositol 3-Kinases · DNA, Neoplasm / analysis · Female · Gene Expression Profiling* · Head and Neck Neoplasms / genetics / mortality / therapy · High-Throughput Nucleotide Sequencing · Humans · Induction Chemotherapy · Male · Medical Records · Middle Aged · Mutation* · Phosphatidylinositol 3-Kinases / genetics · Retrospective Studies · Squamous Cell Carcinoma of Head and Neck · Treatment Outcome · Tumor Suppressor Protein p53 / genetics
- Substances
- DNA, Neoplasm · TP53 protein, human · Tumor Suppressor Protein p53 · Phosphatidylinositol 3-Kinases · Class I Phosphatidylinositol 3-Kinases · PIK3CA protein, human
- 참고문헌
- 29편