Array comparative genomic hybridization in oral cavity (head and neck) squamous cell carcinoma
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ABSTRACT: Genome wide high resolution assay of copy number in a series of frozen, microdissected head and neck cancers originating from the oral cavity. The objective was to characterize areas of amplification and deletion in head and neck cancers arising from the oral cavity subsite. 31 tumors were snap frozen at the time of surgical resection, microdissected to >70% tumor content, and DNA extracted.
Project description:Genome wide high resolution assay of copy number in a series of frozen, microdissected head and neck cancers originating from the oral cavity. The objective was to characterize areas of amplification and deletion in head and neck cancers arising from the oral cavity subsite.
Project description:Oral cavity Squamous Cell Carcinoma (OCSCC) is a common form of head and neck cancer through the developed and developing world. However, the etiology of OCSCC is still unclear. To explore whether smoking, HPV and/or other underlying genetic and transcriptomic changes could be responsible for the oncogenesis events for OCSCC. A prospective observational study of fresh tissue biopsy from 45 participants with OCSCC collected from Brisbane Head and Neck Clinics between 2013 to 2015. Exploration of the genetic and transcriptomic landscape was performed using RNA sequencing and whole exome sequencing. Identification of HPV was to be performed using DNA PCR genotyping and RNA sequencing. Patient medical records were retrieved and the patient demographics were used to correlate with genomic and transcriptomics analyses, including the location of the tumor within the oral cavity, smoking and alcohol histories.
Project description:To understand the diversity of expression states within head and neck cancers, we profiled 5902 single cells from 18 patients with oral cavity tumors by single cell RNA-seq
Project description:Head and neck cancers are a complex malignancy comprising multiple anatomical sites, with cancer of the oral cavity ranking among the deadliest and most disfiguring cancers globally. Oral cancer (OC) constitutes a subset of head and neck cancer cases, presenting primarily as tobacco- and alcohol-associated oral squamous cell carcinoma (OSCC), with a 5-year survival rate of ~65%, partly due to the lack of early detection and effective treatments. OSCC arises from premalignant lesions (PMLs) in the oral cavity through a multi-step series of clinical and histopathological stages, including varying degrees of epithelial dysplasia. To gain insights into the molecular mechanisms associated with the progression of PMLs to OSCC, we profiled the whole transcriptome of 66 human PMLs comprising leukoplakia with dysplasia and hyperkeratosis non-reactive (HkNR) pathologies, alongside healthy controls and OSCC. Our data revealed that PMLs were enriched in gene signatures associated with cellular plasticity, such as partial EMT (p-EMT) phenotypes, and with immune response. Integrated analyses of the host transcriptome and microbiome further highlighted a significant association between differential microbial abundance and PML pathway activity, suggesting a contribution of the oral microbiome towards PML evolution to OSCC. Collectively, this study reveals molecular processes associated with PML progression that may help early diagnosis and disease interception at an early stage.
Project description:Neoadjuvant PD-1 blockade may be efficacious in patients with high-risk, resectable oral-cavity, head-and-neck cancer. To explore correlates of response patterns to neoadjuvant nivolumab treatment and post-surgical recurrences, we analyzed longitudinal tumor and blood samples in a cohort of 12 patients displaying 33% responsiveness. Pretreatment tumor-based detection of FLT4 mutations and PTEN signature enrichment favors response, and high tumor mutational burden improves recurrence-free survival. In contrast, preexisting and/or acquired mutations (in CDKN2A, YAP1, JAK2) correlate with innate resistance and/or tumor recurrence. Immunologically, tumor response after therapy entails T-cell receptor repertoire diversification in peripheral blood and intratumoral expansion of preexisting T-cell clones. A high ratio of regulatory to Th17 T cells in pretreatment blood predicts innate resistance, low cytolytic T-cell signature in pretreatment tumor, and low T-cell receptor repertoire diversity in pretreatment blood. Our study provides a molecular framework to advance neoadjuvant anti-PD-1 therapy for patients with resectable head-and-neck cancer.
Project description:Genome-wide expression array measurements for 9 head and neck squamous cell carcinomas (HNSCC) stratified by worst pattern of invasion (WPOI) Jayakar et al. (2016). Apolipoprotein E promotes invasion in oral squamous cell carcinoma. Li et al. (2013). Validation of the risk model: high-risk classification and tumor pattern of invasion predict outcome for patients with low-stage oral cavity squamous cell carcinoma.
Project description:Microarrays were used to examine gene expression differences between human head and neck squamous cell carcinoma cell lines (FaDu, UTSCC8, UTSCC42a) grown in culture in comparison to a normal oral epithelial cell line. Gene expression data was integrated with global protein expression of head and neck squamous cell carcinoma cell lines and conditioned media to identify secreted protein markers up-regulated at the mRNA level in cancer cells versus the normal cell line. Total RNA obtained from head and neck squamous cell carcinoma cell lines and a normal oral epithelial cell line