scholarly journals Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma

Oncotarget ◽  
2017 ◽  
Vol 8 (11) ◽  
pp. 17684-17699 ◽  
Author(s):  
Tara J. Nulton ◽  
Amy L. Olex ◽  
Mikhail Dozmorov ◽  
Iain M. Morgan ◽  
Brad Windle
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Human Papillomavirus 16 ◽  
Cancer Genome Atlas ◽  
Genome Atlas

scholarly journals Imaging-Genomic Study of Head and Neck Squamous Cell Carcinoma: Associations Between Radiomic Phenotypes and Genomic Mechanisms via Integration of The Cancer Genome Atlas and The Cancer Imaging Archive

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Yitan Zhu ◽  
Abdallah S.R. Mohamed ◽  
Stephen Y. Lai ◽  
Shengjie Yang ◽  
Aasheesh Kanwar ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Tp53 Mutation ◽  
The Cancer Genome Atlas ◽  
Genomic Features ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Purpose Recent data suggest that imaging radiomic features of a tumor could be indicative of important genomic biomarkers. Understanding the relationship between radiomic and genomic features is important for basic cancer research and future patient care. We performed a comprehensive study to discover the imaginggenomic associations in head and neck squamous cell carcinoma (HNSCC) and explore the potential of predicting tumor genomic alternations using radiomic features. Methods Our retrospective study integrated whole-genome multiomics data from The Cancer Genome Atlas with matched computed tomography imaging data from The Cancer Imaging Archive for the same set of 126 patients with HNSCC. Linear regression and gene set enrichment analysis were used to identify statistically significant associations between radiomic imaging and genomic features. Random forest classifier was used to predict the status of two key HNSCC molecular biomarkers, human papillomavirus and disruptive TP53 mutation, on the basis of radiomic features. Results Widespread and statistically significant associations were discovered between genomic features (including microRNA expression, somatic mutations, and transcriptional activity, copy number variations, and promoter region DNA methylation changes of pathways) and radiomic features characterizing the size, shape, and texture of tumor. Prediction of human papillomavirus and TP53 mutation status using radiomic features achieved areas under the receiver operating characteristic curve of 0.71 and 0.641, respectively. Conclusion Our exploratory study suggests that radiomic features are associated with genomic characteristics at multiple molecular layers in HNSCC and provides justification for continued development of radiomics as biomarkers for relevant genomic alterations in HNSCC.

The prognostic value of faciogenital dysplasias as biomarkers in head and neck squamous cell carcinoma

2019 ◽  
Vol 13 (16) ◽  
pp. 1399-1415 ◽  
Author(s):  
Chao Ma ◽  
Haoyu Li ◽  
Xian Li ◽  
Shuwen Lu ◽  
Jianfeng He
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prognostic Value ◽  
The Cancer Genome Atlas ◽  
Gene Expressions ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Aim: This present study aims to investigate the prognostic value of FGD genes for predicting the overall survival in head and neck squamous cell carcinoma (HNSC) patients. Materials & methods: Clinical information and FGD gene expressions of 513 HNSC patients were obtained from The Cancer Genome Atlas dataset. Kaplan–Meier survival, Pearson correlation coefficient analyses and enrichment analyses were performed based on The Cancer Genome Atlas dataset, as well as FGD gene expressions analysis in normal tissues. Results: The survival analyses showed that high levels of FGD2 and FGD3 mRNA expressions, and the combination of high levels of FGD2 and FGD3 mRNAs were associated with the favorable overall survival in HNSC patients (p < 0.01). Oppositely, no significant correlations (p > 0.05) were observed between gender and race and OS. Conclusion: Our findings suggest that the expression levels of FGD2 and FGD3 mRNAs in HNSC are associated with favorable prognosis and may be regarded as potential prognostic biomarkers.

The Cancer Genome Atlas: Integrated analysis of genome alterations in squamous cell carcinoma of the head and neck.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6009-6009 ◽  
Author(s):  
David N. Hayes ◽  
Jennifer R. Grandis ◽  
Adel K. El-Naggar
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Copy Number ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Tumor Subtypes ◽  
Cancer Genome Atlas ◽  
Genome Atlas

6009 Background: Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer death in worldwide. Methods: The Cancer Genome Atlas (TCGA) is conducting DNA, RNA and miRNA sequencing along with DNA copy number profiling, quantification of mRNA expression, promoter methylation, and reverse-phase protein arrays on surgically resected samples from previously untreated patients with HNSCC. We report for the first time the integrated genomic alterations for 279 HNSCC patients. Results: The demographics of 279 patients enrolled in the study show a median age of 61 years (range: 19-90); 27% female, and history of tobacco smoking in 80%. Over 30 sites of significant somatic copy number alteration were identified as well as 15 significantly mutated genes at the false fiscovery rate of <0.01, including: CDKN2A, TP53, PIK3CA, FAT1, MLL2, TGFBR2, HLA-A, NOTCH1, HRAS, NFE2L2, and CASP8. Evidence of the human papilloma virus (HPV) was observed by sequencing in up to 25% of samples. Integrated genomics data supported expected patterns including the predominant role of HPV type 16 infection in nonsmoking patients with tumors of the oropharynx which are wild-type for the tumor suppressor genes p16, Rb, and p53. In addition, striking atypical cases and viral infections will be presented as well as novel anti-correlation of HPV infection with focal copy number alterations including EGFR amplification and chromosome 11q. By contrast co-occurrence of HPV with focal deletions of TRAF3 and mutations of the oncogene PIK3CA will be described. Integrated tumor subtypes defined by gene expression, methylation, and miRNA will be presented in conjunction with associated mutations exclusive to tumor subtypes. For example, alterations of the “antioxidant response elements” transcription activators NFE2L2 and KEAP1 will be documented in association with the “classical” expression subtype of HNSCC, as has been shown in lung squamous cell carcinoma. By contrast, co-occurrence of CASP8 and HRAS will be documented in the “Basal” subtype. Conclusions: While, HNSCC is a heterogeneous tumor, coordinated tumor alterations are observed, including potentially targetable genes and pathways. Results presented on behalf of TCGA.

scholarly journals Decreased expression of cell adhesion genes in cancer stem-like cells isolated from primary oral squamous cell carcinomas

Tumor Biology ◽  
2018 ◽  
Vol 40 (6) ◽  
pp. 101042831878085 ◽  
Author(s):  
Amrendra Mishra ◽  
Harshini Sriram ◽  
Pinal Chandarana ◽  
Vivek Tanavde ◽  
Rekha V Kumar ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Adhesion ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cancer Genome ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

The goal of this study was to isolate cancer stem-like cells marked by high expression of CD44, a putative cancer stem cell marker, from primary oral squamous cell carcinomas and identify distinctive gene expression patterns in these cells. From 1 October 2013 to 4 September 2015, 76 stage III–IV primary oral squamous cell carcinoma of the gingivobuccal sulcus were resected. In all, 13 tumours were analysed by immunohistochemistry to visualise CD44-expressing cells. Expression of CD44 within The Cancer Genome Atlas–Head and Neck Squamous Cell Carcinoma RNA-sequencing data was also assessed. Seventy resected tumours were dissociated into single cells and stained with antibodies to CD44 as well as CD45 and CD31 (together referred as Lineage/Lin). From 45 of these, CD44+Lin– and CD44–Lin– subpopulations were successfully isolated using fluorescence-activated cell sorting, and good-quality RNA was obtained from 14 such sorted pairs. Libraries from five pairs were sequenced and the results analysed using bioinformatics tools. Reverse transcription quantitative polymerase chain reaction was performed to experimentally validate the differential expression of selected candidate genes identified from the transcriptome sequencing in the same 5 and an additional 9 tumours. CD44 was expressed on the surface of poorly differentiated tumour cells, and within the The Cancer Genome Atlas–Head and Neck Squamous Cell Carcinoma samples, its messenger RNA levels were higher in tumours compared to normal. Transcriptomics revealed that 102 genes were upregulated and 85 genes were downregulated in CD44+Lin– compared to CD44–Lin– cells in at least 3 of the 5 tumours sequenced. The upregulated genes included those involved in immune regulation, while the downregulated genes were enriched for genes involved in cell adhesion. Decreased expression of PCDH18, MGP, SPARCL1 and KRTDAP was confirmed by reverse transcription quantitative polymerase chain reaction. Lower expression of the cell–cell adhesion molecule PCDH18 correlated with poorer overall survival in the The Cancer Genome Atlas–Head and Neck Squamous Cell Carcinoma data highlighting it as a potential negative prognostic factor in this cancer.

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