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

  • Chan-Young Ock
  • Bongjun Son
  • Bhumsuk Keam
  • Seung-Youn Lee
  • Jaewoo Moon
  • Hwanjong Kwak
  • Sehui Kim
  • Tae Min Kim
  • Yoon Kyung Jeon
  • Seong Keun Kwon
  • J. Hun Hah
  • Se-Hoon Lee
  • Tack-Kyun Kwon
  • Dong-Wan Kim
  • Hong-Gyun Wu
  • Myung-Whun Sung
  • Dae Seog Heo
Original Article – Clinical Oncology

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

Induction chemotherapy Concurrent chemoradiotherapy Head and neck cancer Survival Targeted gene sequencing 

Notes

Acknowledgments

We thank the patients and their families who generously donated valuable tissue samples.

Funding

This study was supported by SNUH Research Fund (Grant Nos. 04-2013-0760 and 30-2013-0070).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Institutional Review Board of Seoul National University Hospital (approval number: H-1307-051-504) and was conducted in accordance with the principles of the Declaration of Helsinki.

Informed consent

For the patients diagnosed before January 31, 2013, the institutional review board approved the waiver of informed consent for this retrospective analysis according to Bioethics and Safety Act of Korea. For the patients diagnosed after February 1, 2013, we obtained informed consents from the patients.

Supplementary material

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Supplementary material 1 (PDF 56 kb)
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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Chan-Young Ock
    • 1
  • Bongjun Son
    • 2
  • Bhumsuk Keam
    • 1
    • 3
  • Seung-Youn Lee
    • 2
  • Jaewoo Moon
    • 2
  • Hwanjong Kwak
    • 2
  • Sehui Kim
    • 4
  • Tae Min Kim
    • 1
    • 3
  • Yoon Kyung Jeon
    • 4
  • Seong Keun Kwon
    • 3
    • 5
  • J. Hun Hah
    • 3
    • 5
  • Se-Hoon Lee
    • 1
    • 3
  • Tack-Kyun Kwon
    • 5
  • Dong-Wan Kim
    • 1
    • 3
  • Hong-Gyun Wu
    • 6
  • Myung-Whun Sung
    • 3
    • 5
  • Dae Seog Heo
    • 1
    • 3
  1. 1.Department of Internal MedicineSeoul National University HospitalSeoulKorea
  2. 2.TheragenEtex Bio Institute, TheragenEtexSuwonKorea
  3. 3.Cancer Research InstituteSeoul National University College of MedicineSeoulKorea
  4. 4.Department of PathologySeoul National University HospitalSeoulKorea
  5. 5.Department of Otorhinolaryngology-Head and Neck SurgerySeoul National University HospitalSeoulKorea
  6. 6.Department of Radiation OncologySeoul National University HospitalSeoulKorea

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