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

Christine H. Chung; V. B. Guthrie; D. L. Masica; C. Tokheim; H. Kang; J. Richmon; N. Agrawal; C. Fakhry; H. Quon; R. M. Subramaniam; Z. Zuo; T. Seiwert; Z. R. Chalmers; G. M. Frampton; S. M. Ali; R. Yelensky; P. J. Stephens; V. A. Miller; R. Karchin; J. A. Bishop

doi:10.1093/annonc/mdv109

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

Christine H. Chung, V. B. Guthrie, D. L. Masica, C. Tokheim, H. Kang, J. Richmon, N. Agrawal, C. Fakhry, H. Quon, R. M. Subramaniam, Z. Zuo, T. Seiwert, Z. R. Chalmers, G. M. Frampton, S. M. Ali, R. Yelensky, P. J. Stephens, V. A. Miller, R. Karchin, J. A. Bishop

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151 Scopus citations

Abstract

Background: To determine genomic alterations in head and neck squamous cell carcinoma (HNSCC) using formalinfixed, 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 repairp53 and cell cycle pathways in HPV-negative tumors were frequently altered. The HPV-positive oropharynx and HPVpositive 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.

Original language	English (US)
Pages (from-to)	1216-1223
Number of pages	8
Journal	Annals of Oncology
Volume	26
Issue number	6
DOIs	https://doi.org/10.1093/annonc/mdv109
State	Published - Jun 1 2015

Keywords

Copy number variation
DNA mutation
Head and neck squamous cell carcinoma
Human papillomavirus

ASJC Scopus subject areas

Hematology
Oncology

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10.1093/annonc/mdv109

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Chung, C. H., Guthrie, V. B., Masica, D. L., Tokheim, C., Kang, H., Richmon, J., Agrawal, N., Fakhry, C., Quon, H., Subramaniam, R. M., Zuo, Z., Seiwert, T., Chalmers, Z. R., Frampton, G. M., Ali, S. M., Yelensky, R., Stephens, P. J., Miller, V. A., Karchin, R., & Bishop, J. A. (2015). Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing. Annals of Oncology, 26(6), 1216-1223. https://doi.org/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 2015, 'Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing', Annals of Oncology, vol. 26, no. 6, pp. 1216-1223. https://doi.org/10.1093/annonc/mdv109

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title = "Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing",

abstract = "Background: To determine genomic alterations in head and neck squamous cell carcinoma (HNSCC) using formalinfixed, 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 repairp53 and cell cycle pathways in HPV-negative tumors were frequently altered. The HPV-positive oropharynx and HPVpositive 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.",

keywords = "Copy number variation, DNA mutation, Head and neck squamous cell carcinoma, Human papillomavirus",

author = "Chung, {Christine H.} and Guthrie, {V. B.} and Masica, {D. L.} and C. Tokheim and H. Kang and J. Richmon and N. Agrawal and C. Fakhry and H. Quon and Subramaniam, {R. M.} and Z. Zuo and T. Seiwert and Chalmers, {Z. R.} and Frampton, {G. M.} and Ali, {S. M.} and R. Yelensky and Stephens, {P. J.} and Miller, {V. A.} and R. Karchin and Bishop, {J. A.}",

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doi = "10.1093/annonc/mdv109",

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T1 - Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing

AU - Chung, Christine H.

AU - Guthrie, V. B.

AU - Masica, D. L.

AU - Tokheim, C.

AU - Kang, H.

AU - Richmon, J.

AU - Agrawal, N.

AU - Fakhry, C.

AU - Quon, H.

AU - Subramaniam, R. M.

AU - Zuo, Z.

AU - Seiwert, T.

AU - Chalmers, Z. R.

AU - Frampton, G. M.

AU - Ali, S. M.

AU - Yelensky, R.

AU - Stephens, P. J.

AU - Miller, V. A.

AU - Karchin, R.

AU - Bishop, J. A.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Background: To determine genomic alterations in head and neck squamous cell carcinoma (HNSCC) using formalinfixed, 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 repairp53 and cell cycle pathways in HPV-negative tumors were frequently altered. The HPV-positive oropharynx and HPVpositive 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.

AB - Background: To determine genomic alterations in head and neck squamous cell carcinoma (HNSCC) using formalinfixed, 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 repairp53 and cell cycle pathways in HPV-negative tumors were frequently altered. The HPV-positive oropharynx and HPVpositive 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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Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing

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