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Identification of genomic mutations associated with clinical outcomes of induction chemotherapy in patients with head and neck squamous cell carcinoma

Cited 9 time in Web of Science Cited 10 time in Scopus
Authors
Ock, Chan-Young; Son, Bongjun; Keam, Bhumsuk; Lee, Seung-Youn; Moon, Jaewoo; Kwak, Hwanjong; Kim, Sehui; Kim, Tae Min; Jeon, Yoon Kyung; Kwon, Seong Keun; Hah, J. Hun; Lee, Se-Hoon; Kwon, Tack-Kyun; Kim, Dong-Wan; Wu, Hong-Gyun; Sung, Myung-Whun; Heo, Dae Seog
Issue Date
2016-04
Citation
Journal of Cancer Research and Clinical Oncology, Vol.142 No.4, pp.873-883
Keywords
Induction chemotherapyConcurrent chemoradiotherapyHead and neck cancerSurvivalTargeted gene sequencing
Abstract
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. 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 %. 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). 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.
ISSN
0171-5216
URI
http://hdl.handle.net/10371/165328
DOI
https://doi.org/10.1007/s00432-015-2083-2
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College of Medicine/School of Medicine (의과대학/대학원)Cancer Research Institute (암연구소)Journal Papers (저널논문_암연구소)
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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