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PIK3CA and p53 mutations promote 4NQO-initated head and neck tumor progression and metastasis in mice

ABSTRACT: PIK3CA and p53 mutations promote 4NQO-initated head and neck tumor progression and metastasis in mice

PROVIDER: PRJNA601436 | ENA |

REPOSITORIES: ENA

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PIK3CA and p53 mutations promote 4NQO-initated head and neck tumor progression and metastasis in mice

Project description:The effect of gain of function mutations in p53, pik3ca, and both genes in mouse tongue subject to 4NQO treatment on gene expression is characterized by RNASeq.

2022-04-19 | GSE143716 | GEO

A head and neck cancer protein interaction map reveals PIK3CA mutant drug sensitivity

Project description:Despite extensive DNA sequencing of patient tumors, it remains challenging to translate the immense landscape of heterogeneous genetic alterations into function and clinical outcomes due to a limited understanding of cancer specific molecular network architectures. To bridge this gap, we have used affinity purification-mass spectrometry to generate protein interaction networks for 31 proteins with significant alterations in head and neck squamous cell carcinoma. This network includes 771 interactions covering both cancer and non-tumorigenic cell states, as well as wild-type and mutant proteins. Differential analysis across these dimensions reveals a strong interaction between PIK3CA and ERBB3 (HER3), dependent upon mutations in PIK3CA. We show that this interaction correlates with ERBB3 activity in vitro and can be targeted in vivo using a clinical ERBB3 inhibitor, CDX3379, to prohibit growth of tumors with common PIK3CA mutations. This study provides a roadmap for elucidating genetic complexity through multidimensional maps of cancer cell biology.

2021-10-07 | PXD019469 | Pride

Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated with poor outcome and activation of the YAP pathway

Project description:Objectives: Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) is commonly altered in many human tumors, leading to the activation of p110α enzymatic activity that stimulates growth factor-independent cell growth. PIK3CA alterations such as mutation, gene amplification and overexpression are common in head and neck squamous cell carcinoma (HNSCC) and. We aim to explore how these alterations and clinical outcome are associated, as well as the molecular mechanisms involved. Material and methods: Mutation and copy-number variation in PIK3CA, and whole-genome expression profiles, were analyzed in primary HNSCC tumors from The Cancer Genome Atlas (TCGA) cohort (n=243). The results were validated in an independent cohort form the University Hospital of A Coruña (UHAC, n=62). Expression of the PIK3CA gene protein product (PI3K p110α) and nuclear YAP were assessed in tissue microarrays in a cohort from the University Hospital 12 de Octubre (UH12O, n=91). Results: Only high expression of the PIK3CA gene was associated with poor clinical outcome. The study of gene expression, transcription factor and protein signatures suggested that the activation of the Hippo-YAP pathway, involved in organ size, stem cell maintenance and tumorigenesis, could underlie tumor progression in PI3KCA overexpressing tumors. Tissue arrays showed that PI3K p110α levels correlated with YAP nuclear localization in HNSCC tumors. Conclusions: High expression of PIK3CA in HNSCC primary tumors identifies patients at high risk for recurrence. In these tumors, progression could rely on the Hippo-YAP pathway instead of the canonical Akt/mTOR pathway. This observation could have important implications in the therapeutic options for patients.

2018-04-02 | GSE95805 | GEO

Head and neck squamous cell carcinoma

Project description:Quantitative (iTRAQ 4-plex) proteomic analysis of progressive head and neck cancers

2022-03-01 | PXD001438 | Pride

Gene expression profiles of head and neck squamous cell carcinoma

Project description:Sage performed on microdissection of Head and Neck tumor, and Head and Neck normal tissue comparative analysis of gene expression profiles of head and neck squamous cell carcinoma and Head and Neck normal tissue

2008-09-30 | E-GEOD-11986 | biostudies-arrayexpress

Gene expression profiles of head and neck squamous cell carcinoma

Project description:Sage performed on microdissection of Head and Neck tumor, and Head and Neck normal tissue

2008-09-30 | GSE11986 | GEO

Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: normal head and neck tissue

Project description:Genome-wide DNA methylation profiling of head and neck squamous cell carcinomas. The Illumina Infinium 27k Human DNA methylation BeadChip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in fresh-frozen tumor tissues. Samples included 91 tumors from the oralpharynx and larynx, reflecting all stages of disease, 18 normal head and neck National Disease Research Interchange (NDRI) samples, and 213 normal control blood samples. Bisulphite-converted DNA from the 18 normal head and neck samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.

2011-10-27 | E-GEOD-25083 | biostudies-arrayexpress

RNA-seq of head and neck cell lines

Project description:Two HPV(+) head and neck cancer cell lines (UPCI-SCC-090, UM-SCC-104), one HPV(–) head and neck cancer cell line (FaDu) and one nasopharyngeal epithelial cell line (NP69SV40T) were subjected to RNA-seq analysis.

2023-01-06 | GSE211322 | GEO

Subtypes of HPV-positive head and neck cancers are associated with HPV characteristics, copy number variations, PIK3CA mutation, and pathway signatures. [RNA-Seq]

Project description:Purpose: There is substantial heterogeneity within the human papillomavirus (HPV) positive head and neck cancer (HNC) tumors that predispose them to different outcomes, however this subgroup is poorly characterized due to various historical reasons. Experimental Design: we perform unsupervised gene expression clustering on well-annotated HPV(+) HNC samples from two cohorts ( 84 total primary tumors), as well as 18 HPV(-) HNCs, to discover subtypes, and begin to characterize the differences between the subtypes in terms of their HPV characteristics, pathway activity, whole-genome somatic copy number variations and mutation frequencies. Results: We identified two distinctive HPV(+) subtypes by unsupervised clustering. Membership in the HPV(+) subtypes correlates with genic viral integration status, E2/E4/E5 expression levels and the ratio of spliced to full length HPV oncogene E6. The subtypes also show differences in copy number alterations, in particular the loss of chr16q and gain of chr3q, PIK3CA mutation, and in the expression of genes involved in several biological processes related to cancer, including immune response, oxidation-reduction process, and keratinocyte and mesenchymal differentiation. Conclusion: Our characterization of two subtypes of HPV(+) tumors provides valuable molecular level information in relation to the alternative paths to tumor development and to that of HPV(-) HNCs. Together, these results will shed light on stratifications of the HPV(+) HNCs and will help to guide personalized care for HPV(+) HNC patients. 36 head and neck primary tumors (18 HPV+ and 18 HPV-) and their matched blood samples were collected and genotyped by Illumina OmniExpress SNP array. RNA-seq was also performed on the same set of tumor samples.

2016-05-13 | E-GEOD-74927 | biostudies-arrayexpress