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Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing.

Publication ,  Journal Article
Chung, CH; Guthrie, VB; Masica, DL; Tokheim, C; Kang, H; Richmon, J; Agrawal, N; Fakhry, C; Quon, H; Subramaniam, RM; Zuo, Z; Seiwert, T ...
Published in: Ann Oncol
June 2015

BACKGROUND: To determine genomic alterations in head and neck squamous cell carcinoma (HNSCC) using formalin-fixed, paraffin-embedded (FFPE) tumors obtained through routine clinical practice, selected cancer-related genes were evaluated and compared with alterations seen in frozen tumors obtained through research studies. PATIENTS AND METHODS: DNA samples obtained from 252 FFPE HNSCC were analyzed using next-generation sequencing-based (NGS) clinical assay to determine sequence and copy number variations in 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. Human papillomavirus (HPV) status was determined by presence of the HPV DNA sequence in all samples and corroborated with high-risk HPV in situ hybridization (ISH) and p16 immunohistochemical (IHC) staining in a subset of tumors. Sequencing data from 399 frozen tumors in The Cancer Genome Atlas and University of Chicago public datasets were analyzed for comparison. RESULTS: Among 252 FFPE HNSCC, 84 (33%) were HPV positive and 168 (67%) were HPV negative by sequencing. A subset of 40 tumors with HPV ISH and p16 IHC results showed complete concordance with NGS-derived HPV status. The most common genes with genomic alterations were PIK3CA and PTEN in HPV-positive tumors and TP53 and CDKN2A/B in HPV-negative tumors. In the pathway analysis, the PI3K pathway in HPV-positive tumors and DNA repair-p53 and cell cycle pathways in HPV-negative tumors were frequently altered. The HPV-positive oropharynx and HPV-positive nasal cavity/paranasal sinus carcinoma shared similar mutational profiles. CONCLUSION: The genomic profile of FFPE HNSCC tumors obtained through routine clinical practice is comparable with frozen tumors studied in research setting, demonstrating the feasibility of comprehensive genomic profiling in a clinical setting. However, the clinical significance of these genomic alterations requires further investigation through application of these genomic profiles as integral biomarkers in clinical trials.

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Published In

Ann Oncol

DOI

EISSN

1569-8041

Publication Date

June 2015

Volume

26

Issue

6

Start / End Page

1216 / 1223

Location

England

Related Subject Headings

  • Tissue Fixation
  • Squamous Cell Carcinoma of Head and Neck
  • Prognosis
  • Predictive Value of Tests
  • Phenotype
  • Paraffin Embedding
  • Papillomaviridae
  • Oncology & Carcinogenesis
  • Mutation
  • Middle Aged
 

Citation

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Chung, C. H., Guthrie, V. B., Masica, D. L., Tokheim, C., Kang, H., Richmon, J., … Bishop, J. A. (2015). Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing. Ann Oncol, 26(6), 1216–1223. https://doi.org/10.1093/annonc/mdv109
Chung, C. H., V. B. Guthrie, D. L. Masica, C. Tokheim, H. Kang, J. Richmon, N. Agrawal, et al. “Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing.Ann Oncol 26, no. 6 (June 2015): 1216–23. https://doi.org/10.1093/annonc/mdv109.
Chung CH, Guthrie VB, Masica DL, Tokheim C, Kang H, Richmon J, et al. Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing. Ann Oncol. 2015 Jun;26(6):1216–23.
Chung, C. H., et al. “Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing.Ann Oncol, vol. 26, no. 6, June 2015, pp. 1216–23. Pubmed, doi:10.1093/annonc/mdv109.
Chung CH, Guthrie VB, Masica DL, Tokheim C, Kang H, Richmon J, Agrawal N, Fakhry C, Quon H, Subramaniam RM, Zuo Z, Seiwert T, Chalmers ZR, Frampton GM, Ali SM, Yelensky R, Stephens PJ, Miller VA, Karchin R, Bishop JA. Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing. Ann Oncol. 2015 Jun;26(6):1216–1223.
Journal cover image

Published In

Ann Oncol

DOI

EISSN

1569-8041

Publication Date

June 2015

Volume

26

Issue

6

Start / End Page

1216 / 1223

Location

England

Related Subject Headings

  • Tissue Fixation
  • Squamous Cell Carcinoma of Head and Neck
  • Prognosis
  • Predictive Value of Tests
  • Phenotype
  • Paraffin Embedding
  • Papillomaviridae
  • Oncology & Carcinogenesis
  • Mutation
  • Middle Aged