Machine learning with the cancer genome atlas head and neck squamous cell carcinoma dataset

2019 ◽  
Author(s):  
Michael Rendleman
Keyword(s):  
Machine Learning ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cancer Genome ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

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.

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.

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