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Comprehensive genomic profiling of head and neck squamous cell carcinoma reveals FGFR1 amplifications and tumour genomic alterations burden as prognostic biomarkers of survival.
Eur J Cancer. 2018 03; 91:47-55.EJ

Abstract

BACKGROUND

We aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value.

PATIENTS AND METHODS

We retrieved 122 HNSCC patients who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis. Univariate and multivariate analyses were performed to assess the prognostic value of altered genes.

RESULTS

A median of 2 (range: 0-10) genomic alterations per sample was observed. Most frequently altered genes involved the cell cycle pathway (TP53 [60%], CCND1 [30%], CDKN2A [25%]), the PI3K/AKT/MTOR pathway (PIK3CA [12%]), tyrosine kinase receptors (EGFR [9%], FGFR1 [5%]) and cell differentiation (FAT1 [7%], NOTCH1 [4%]). TP53 mutations (p = 0.003), CCND1 amplifications (p = 0.04), CDKN2A alterations (p = 0.02) and FGFR1 amplifications (p = 0.003), correlated with shorter overall survival (OS). The number of genomic alterations was significantly higher in the HPV-negative population (p = 0.029) and correlated with a shorter OS (p < 0.0001). Only TP53 mutation and FGFR1 amplification status remained statistically significant in the multivariate analysis.

CONCLUSION

These results suggest that genomic alterations involving the cell cycle (TP53, CCND1, CDKN2A), as well as FGFR1 amplifications and tumour genomic alterations burden are prognostic biomarkers and might be therapeutic targets for patients with HNSCC.

Authors+Show Affiliations

Department of Medical Oncology, Institut Curie, Paris, Saint-Cloud, France; Unit of Pharmacogenomics, Department of Genetics, Institut Curie, Paris, France. Electronic address: coraline.dubot@curie.fr.Unit of Bioinformatics, Next Generation Sequencing Platform-ICGex, Institut Curie, Paris, France.Department of Medical Oncology, Institut Curie, Paris, Saint-Cloud, France.Unit of Pharmacogenomics, Department of Genetics, Institut Curie, Paris, France.Unit of Pharmacogenomics, Department of Genetics, Institut Curie, Paris, France.Unit of Pharmacogenomics, Department of Genetics, Institut Curie, Paris, France.Unit of Somatic Genomics, Department of Genetics, Institut Curie, Paris, France.Unit of Somatic Genomics, Department of Genetics, Institut Curie, Paris, France.Unit of Bioinformatics, Next Generation Sequencing Platform-ICGex, Institut Curie, Paris, France.Department of Biopathology, Institut Curie, Paris, France.Department of Biopathology, Institut Curie, Paris, France.Department of Biopathology, Institut Curie, Paris, France.Department of Surgery, Institut Curie, Paris, France.Department of Radiotherapy, Institut Curie, Paris, France.Department of Surgery, Institut Curie, Paris, France.Department of Surgery, Institut Curie, Paris, France.Department of Surgery, Institut Curie, Paris, France.Department of Biostatistics, Institut Curie, Paris, France.Department of Medical Oncology, Institut Curie, Paris, Saint-Cloud, France; INSERM U900 Research Unit, Saint-Cloud, France.Department of Medical Oncology, Institut Curie, Paris, Saint-Cloud, France.Unit of Pharmacogenomics, Department of Genetics, Institut Curie, Paris, France; EA7331, Paris Descartes University, Faculty of Pharmaceutical and Biological Sciences, Paris, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29331751

Citation

Dubot, C, et al. "Comprehensive Genomic Profiling of Head and Neck Squamous Cell Carcinoma Reveals FGFR1 Amplifications and Tumour Genomic Alterations Burden as Prognostic Biomarkers of Survival." European Journal of Cancer (Oxford, England : 1990), vol. 91, 2018, pp. 47-55.
Dubot C, Bernard V, Sablin MP, et al. Comprehensive genomic profiling of head and neck squamous cell carcinoma reveals FGFR1 amplifications and tumour genomic alterations burden as prognostic biomarkers of survival. Eur J Cancer. 2018;91:47-55.
Dubot, C., Bernard, V., Sablin, M. P., Vacher, S., Chemlali, W., Schnitzler, A., Pierron, G., Ait Rais, K., Bessoltane, N., Jeannot, E., Klijanienko, J., Mariani, O., Jouffroy, T., Calugaru, V., Hoffmann, C., Lesnik, M., Badois, N., Berger, F., Le Tourneau, C., ... Bieche, I. (2018). Comprehensive genomic profiling of head and neck squamous cell carcinoma reveals FGFR1 amplifications and tumour genomic alterations burden as prognostic biomarkers of survival. European Journal of Cancer (Oxford, England : 1990), 91, 47-55. https://doi.org/10.1016/j.ejca.2017.12.016
Dubot C, et al. Comprehensive Genomic Profiling of Head and Neck Squamous Cell Carcinoma Reveals FGFR1 Amplifications and Tumour Genomic Alterations Burden as Prognostic Biomarkers of Survival. Eur J Cancer. 2018;91:47-55. PubMed PMID: 29331751.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comprehensive genomic profiling of head and neck squamous cell carcinoma reveals FGFR1 amplifications and tumour genomic alterations burden as prognostic biomarkers of survival. AU - Dubot,C, AU - Bernard,V, AU - Sablin,M P, AU - Vacher,S, AU - Chemlali,W, AU - Schnitzler,A, AU - Pierron,G, AU - Ait Rais,K, AU - Bessoltane,N, AU - Jeannot,E, AU - Klijanienko,J, AU - Mariani,O, AU - Jouffroy,T, AU - Calugaru,V, AU - Hoffmann,C, AU - Lesnik,M, AU - Badois,N, AU - Berger,F, AU - Le Tourneau,C, AU - Kamal,M, AU - Bieche,I, Y1 - 2018/01/11/ PY - 2017/09/08/received PY - 2017/11/25/revised PY - 2017/12/09/accepted PY - 2018/1/15/pubmed PY - 2018/10/24/medline PY - 2018/1/15/entrez KW - Clinical prognostic and theragnostic biomarkers KW - Head and neck squamous cell carcinoma KW - Next generation sequencing SP - 47 EP - 55 JF - European journal of cancer (Oxford, England : 1990) JO - Eur. J. Cancer VL - 91 N2 - BACKGROUND: We aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value. PATIENTS AND METHODS: We retrieved 122 HNSCC patients who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis. Univariate and multivariate analyses were performed to assess the prognostic value of altered genes. RESULTS: A median of 2 (range: 0-10) genomic alterations per sample was observed. Most frequently altered genes involved the cell cycle pathway (TP53 [60%], CCND1 [30%], CDKN2A [25%]), the PI3K/AKT/MTOR pathway (PIK3CA [12%]), tyrosine kinase receptors (EGFR [9%], FGFR1 [5%]) and cell differentiation (FAT1 [7%], NOTCH1 [4%]). TP53 mutations (p = 0.003), CCND1 amplifications (p = 0.04), CDKN2A alterations (p = 0.02) and FGFR1 amplifications (p = 0.003), correlated with shorter overall survival (OS). The number of genomic alterations was significantly higher in the HPV-negative population (p = 0.029) and correlated with a shorter OS (p < 0.0001). Only TP53 mutation and FGFR1 amplification status remained statistically significant in the multivariate analysis. CONCLUSION: These results suggest that genomic alterations involving the cell cycle (TP53, CCND1, CDKN2A), as well as FGFR1 amplifications and tumour genomic alterations burden are prognostic biomarkers and might be therapeutic targets for patients with HNSCC. SN - 1879-0852 UR - https://www.unboundmedicine.com/medline/citation/29331751/Comprehensive_genomic_profiling_of_head_and_neck_squamous_cell_carcinoma_reveals_FGFR1_amplifications_and_tumour_genomic_alterations_burden_as_prognostic_biomarkers_of_survival_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0959-8049(17)31495-8 DB - PRIME DP - Unbound Medicine ER -