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Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing.
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.
Afiliación
  • Chung CH; Department of Oncology; Department of Otolaryngology-Head and Neck Surgery. Electronic address: cchung11@jhmi.edu.
  • Guthrie VB; Department of Biomedical Engineering, Institute for Computational Medicine.
  • Masica DL; Department of Biomedical Engineering, Institute for Computational Medicine.
  • Tokheim C; Department of Biomedical Engineering, Institute for Computational Medicine.
  • Kang H; Department of Oncology.
  • Richmon J; Department of Otolaryngology-Head and Neck Surgery.
  • Agrawal N; Department of Otolaryngology-Head and Neck Surgery.
  • Fakhry C; Department of Oncology; Department of Otolaryngology-Head and Neck Surgery; Department of Milton J. Dance Head and Neck Center, Baltimore.
  • Quon H; Department of Radiation Oncology.
  • Subramaniam RM; Department of Oncology; Department of Otolaryngology-Head and Neck Surgery; Department of Radiology and Radiological Sciences.
  • Zuo Z; Department of Medicine, University of Chicago, Chicago.
  • Seiwert T; Department of Medicine, University of Chicago, Chicago.
  • Chalmers ZR; Foundation Medicine, Inc., Cambridge, USA.
  • Frampton GM; Foundation Medicine, Inc., Cambridge, USA.
  • Ali SM; Foundation Medicine, Inc., Cambridge, USA.
  • Yelensky R; Foundation Medicine, Inc., Cambridge, USA.
  • Stephens PJ; Foundation Medicine, Inc., Cambridge, USA.
  • Miller VA; Foundation Medicine, Inc., Cambridge, USA.
  • Karchin R; Department of Oncology; Department of Biomedical Engineering, Institute for Computational Medicine.
  • Bishop JA; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore.
Ann Oncol ; 26(6): 1216-1223, 2015 Jun.
Article en En | MEDLINE | ID: mdl-25712460
ABSTRACT

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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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carcinoma de Células Escamosas / Biomarcadores de Tumor / Perfilación de la Expresión Génica / Secuenciación de Nucleótidos de Alto Rendimiento / Neoplasias de Cabeza y Cuello Tipo de estudio: Prognostic_studies Límite: Aged80 Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2015 Tipo del documento: Article
Texto completo
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Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carcinoma de Células Escamosas / Biomarcadores de Tumor / Perfilación de la Expresión Génica / Secuenciación de Nucleótidos de Alto Rendimiento / Neoplasias de Cabeza y Cuello Tipo de estudio: Prognostic_studies Límite: Aged80 Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2015 Tipo del documento: Article