Genetic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing
Menée sur 252 échantillons tumoraux fixés au formol et inclus en paraffine après prélèvement sur des patients atteints d'un carcinome épidermoïde de la tête et du cou, et à partir de données issues du projet "The Cancer Genome Atlas" (399 échantillons tumoraux congelés), cette étude montre que le profil génétique des tumeurs recueillies en pratique clinique de routine est comparable à celui des tumeurs recueillies dans le cadre d'un projet de recherche
Background : To determine genetic 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 staining (IHC) 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 genetic 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 genetic profile of FFPE HNSCC tumors obtained through routine clinical practice is comparable to frozen tumors studied in research setting, demonstrating the feasibility of comprehensive genomic profiling in a clinical setting. However, the clinical significance of these genetic alterations requires further investigation through application of these genomic profiles as integral biomarkers in clinical trials.
Annals of Oncology , résumé, 2015