Project description:Despite aggressive multi-modal treatment, advanced head and neck squamous cell carcinoma (HNSCC) patients are at high risk of recurrence. Matched pairs (n=38) of primary/recurrent tumors were subjected to whole exome and RNA sequencing. Mutational landscapes and genomic copy number alterations indicated diverging clonal origins in a subset of cases. Transcriptional subtyping (classical/CL, basal/BA, inflamed-mesenchymal/IMS) in primary and recurrent HNSCC (n=112) revealed more frequent CL and IMS in primary tumors with low recurrence rates and a prevalence of BA in recurrent tumors associated with p-EMT and early recurrence. 44% of matched cases underwent a subtype change from primary to recurrent tumors, preferably from IMS to BA or CL. In recurrences, HYPOXIA, P-EMT and RADIATION RESISTANCE signatures were up- and TUMOR INFLAMMATION down-regulated compared to index tumors. A therapy-induced selection of transcriptional subtypes demonstrates the importance of molecular characterization of recurrences for second-line therapy decisions to enable optimally tailored treatments.
Project description:Despite aggressive multi-modal treatment, advanced head and neck squamous cell carcinoma (HNSCC) patients are at high risk of recurrence. Matched pairs (n=38) of primary/recurrent tumors were subjected to whole exome and RNA sequencing. Mutational landscapes and genomic copy number alterations indicated diverging clonal origins in a subset of cases. Transcriptional subtyping (classical/CL, basal/BA, inflamed-mesenchymal/IMS) in primary and recurrent HNSCC (n=112) revealed more frequent CL and IMS in primary tumors with low recurrence rates and a prevalence of BA in recurrent tumors associated with p-EMT and early recurrence. 44% of matched cases underwent a subtype change from primary to recurrent tumors, preferably from IMS to BA or CL. In recurrences, HYPOXIA, P-EMT and RADIATION RESISTANCE signatures were up- and TUMOR INFLAMMATION down-regulated compared to index tumors. A therapy-induced selection of transcriptional subtypes demonstrates the importance of molecular characterization of recurrences for second-line therapy decisions to enable optimally tailored treatments.
Project description:Despite aggressive multi-modal treatment, advanced head and neck squamous cell carcinoma (HNSCC) patients are at high risk of recurrence. n=19 different selected areas of matched pairs (n=3) of primary/recurrent tumor specimens were subjected to RNA sequencing. Transcriptional subtyping (classical/CL, basal/BA, inflamed-mesenchymal/IMS) in matched primary and recurrent HNSCC specimens revealed heterogeneity.
Project description:To look at genes/pathways differentially expressed in metastatic and primary tumor cells we performed global gene expression profiling of the 3 sets of HNSCC lines derived from primary tumors and matched metastatic sites. Illumina HT-12 v4 BeadChip arrays were used. The data suggest that HNSCC lines derived from metastatic sites exhibit phenotypes distinct from those found in cells derived from the corresponding primary tumors. Metastatic cell lines upregulated several pathways involved in stem cell self-renewal, invasion and migration, which are well known characteristics of metastatic progression. We conclude that the cell lines derived from primary patient tumors and matched metastatic sites represent a reliable model to study HNSCC metastasis.
Project description:This study focused on global methylation changes between tumors, normal mucosa, primary tumor xenografts, and cell lines in order to determine epigenetic changes in cell cultures and xenografts derived from primary tumors. 1 fully methylated control cell line, 1 fully demethylated control cell line, 5 HNSCC cell lines, 2 normal cell lines, 7 normal mucosa, 3 primary HNSCC tumors, 3 xenografts of primary tumors
Project description:60 fresh frozen HNSCC from the University of North Carolina at Chapel Hill (UNC) were obtained from the UNC Tissue Procurement Facility under an IRB approved protocol. 55 tumor samples were collected from the primary tumor and five tumor samples were collected from a local recurrence at the primary site; one tumor also had a sample of the primary tumor and an associated lymph node metastasis . In addition, we profiled three normal tonsillar epithelium samples that were collected from three pediatric patients following routine tonsillectomy and four HNSCC tumor derived cell lines (UNC7, UMSCCA1, CAL27 and JHU022). Each experimental sample (tumor, normal or cell line) was assayed versus a â??common referenceâ?? sample that was a pool of total RNA derived from 30 of the HNSCC samples. This tumor pool reference strategy has been successfully used in another profiling study. In total, 78 experiments were performed, which utilized three separate preparations of the common reference pool. Keywords = Head and neck cancer Keywords = gene expression profiles Keywords = microarray