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Transcriptomic characterization of paired primary and recurrent HNSCC tumors

ABSTRACT: Transcriptomic characterization of paired primary and recurrent HNSCC tumors

PROVIDER: PRJNA727315 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14428032_1.fastq.gz	Fastqsanger.gz
	SRR14428032_2.fastq.gz	Fastqsanger.gz
	SRR14428033_1.fastq.gz	Fastqsanger.gz
	SRR14428033_2.fastq.gz	Fastqsanger.gz
	SRR14428034_1.fastq.gz	Fastqsanger.gz

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Transcriptomic characterization of paired primary and recurrent HNSCC tumors

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.

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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.

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Multi-omics profiling of paired primary and recurrent glioblastoma patient tissues

Project description:Background Despite maximal therapy with surgery, chemotherapy and radiotherapy, glioblastoma multiforme (GBM) patients have a median survival of only 15 months. Almost all patients inevitably experience symptomatic tumor recurrence. A hallmark of this tumor type is the large heterogeneity between patients and within tumors itself which relate to failure of standardized tumor treatment. In this study, tissue samples of paired primary and recurrent GBM tumors were investigated to identify individual factors related to tumor progression. Methods Paired primary and recurrent GBM tumor tissues from 8 patients were investigated with a multi-omics approach using transcriptomics, proteomics and phosphoproteomics. Results In the studied patient cohort, large variations between and within patients are observed for all omics analyses. A few pathways affected at the different omics levels partly overlapped if patients are analyzed at the individual level, such as synaptogenesis (containing the SNARE complex) and cholesterol metabolism. Phosphoproteomics revealed increased STMN1(S38) phosphorylation that relates to ERBB4 signaling. A pathway tool has been developed to visualize and compare the different omics datasets per patient and showed potential therapeutic drugs, such as abobotulinumtoxina and afatinib, that target these affected pathways. Afatinib targeting ERBB4 signaling is currently in clinical trials for GBM. Conclusions Large variation on all omics levels exist between and within GBM patients. Therefore, it will be rather unlikely to find a drug treatment that would fit all patients. Instead a multi-omics approach can be used to identify affected pathways on the individual patient level and select potential treatment options.

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