Detection of viral gene expression in risk‐stratified biopsies reveals no active HPV in cutaneous squamous cell carcinoma

2021 ◽  
Author(s):  
Amy R. Vandiver ◽  
Brandon J. Thomas ◽  
Mohammad Karimzada ◽  
Byron C. Knowles ◽  
Giovanni A. Botten ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Viral Gene Expression ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Viral Gene

scholarly journals Methyltransferases in the Pathogenesis of Keratinocyte Cancers

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3402
Author(s):  
Eun Kyung Ko ◽  
Brian C. Capell
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Basal Cell ◽  
Histone Methylation ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Therapeutic Approaches ◽  
Novel Therapeutic

Recent evidence suggests that the disruption of gene expression by alterations in DNA, RNA, and histone methylation may be critical contributors to the pathogenesis of keratinocyte cancers (KCs), made up of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), which collectively outnumber all other human cancers combined. While it is clear that methylation modifiers are frequently dysregulated in KCs, the underlying molecular and mechanistic changes are only beginning to be understood. Intriguingly, it has recently emerged that there is extensive cross-talk amongst these distinct methylation processes. Here, we summarize and synthesize the latest findings in this space and highlight how these discoveries may uncover novel therapeutic approaches for these ubiquitous cancers.

scholarly journals Comprehensive Mutational and Phenotypic Characterization of New Metastatic Cutaneous Squamous Cell Carcinoma Cell Lines Reveal Novel Drug Susceptibilities

2020 ◽  
Vol 21 (24) ◽  
pp. 9536
Author(s):  
Jay Perry ◽  
Bruce Ashford ◽  
Amarinder Singh Thind ◽  
Marie-Emilie Gauthier ◽  
Elahe Minaei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Phenotypic Characterization ◽  
Adjuvant Radiation ◽  
Compound Libraries ◽  
Novel Drug

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Most patients who develop metastases (2–5%) present with advanced disease that requires a combination of radical surgery and adjuvant radiation therapy. There are few effective therapies for refractory disease. In this study, we describe novel patient-derived cell lines from cSCC metastases of the head and neck (designated UW-CSCC1 and UW-CSCC2). The cell lines genotypically and phenotypically resembled the original patient tumor and were tumorogenic in mice. Differences in cancer-related gene expression between the tumor and cell lines after various culturing conditions could be largely reversed by xenografting and reculturing. The novel drug susceptibilities of UW-CSCC1 and an irradiated subclone UW-CSCC1-R to drugs targeting cell cycle, PI3K/AKT/mTOR, and DNA damage pathways were observed using high-throughput anti-cancer and kinase-inhibitor compound libraries, which correlate with either copy number variations, targetable mutations and/or the upregulation of gene expression. A secondary screen of top hits in all three cell lines including PIK3CA-targeting drugs supports the utility of targeting the PI3K/AKT/mTOR pathway in this disease. UW-CSCC cell lines are thus useful preclinical models for determining targetable pathways and candidate therapeutics.

scholarly journals Analytical validity of DecisionDx-SCC, a gene expression profile test to identify risk of metastasis in cutaneous squamous cell carcinoma (SCC) patients

2021 ◽  
Author(s):  
Sherri Borman ◽  
Jeff Wilkinson ◽  
Lauren Meldi-Sholl ◽  
Clare Johnson ◽  
Kelsey Carter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Risk Class ◽  
Class 1

Abstract Background To improve identification of patients with cutaneous squamous cell carcinoma (SCC) at high risk for metastatic disease, the DecisionDx-SCC assay, a prognostic 40-gene expression profile (40-GEP) test, was developed and validated. The 40-GEP assay utilizes RT-PCR gene expression analysis on primary tumor biopsy tissue to evaluate the expression of 34 signature gene targets and 6 normalization genes. The test provides classifications of low risk (Class 1), moderate risk (Class 2A), and high risk (Class 2B) of metastasis within 3 years of diagnosis. The primary objective of this study was to validate the analytical performance of the 40 gene expression signature. Methods The repeatability and reproducibility of the 40-GEP test was evaluated by performance of inter-assay, intra-assay, and inter-operator precision experiments along with monitoring the reliability of sample and reagent stability for class call concordance. The technical performance of clinical orders from September 2020 through July 2021 for the 40-GEP test was assessed. Results Patient hematoxylin and eosin (H&E) stained slides were reviewed by a board-certified pathologist to assess minimum acceptable tumor content. Class specific controls (Class 1 and Class 2B) were evaluated with Levey Jennings analysis and demonstrated consistent and reproducible results. Inter-assay, inter-operator and intra-assay concordance were all ≥90%, with short-term and long-term RNA stability also meeting minimum concordance requirements. Of the 2,446 orders received, 93.4% remained eligible for testing, with 96.8% of all tested samples that completed the assay demonstrating actionable class call results. Conclusion DecisionDx-SCC demonstrates a high degree of analytical precision, yielding high concordance rates across multiple performance experiments, along with exhibiting robust technical reliability on clinical samples.

scholarly journals Reprogramming and Differentiation of Cutaneous Squamous Cell Carcinoma Cells in Recessive Dystrophic Epidermolysis Bullosa

2020 ◽  
Vol 22 (1) ◽  
pp. 245
Author(s):  
Avina Rami ◽  
Łukasz Łaczmański ◽  
Jagoda Jacków-Nowicka ◽  
Joanna Jacków
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epidermolysis Bullosa ◽  
Expression Profiles ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Rapid Progression ◽  
Dystrophic Epidermolysis Bullosa ◽  
Recessive Dystrophic Epidermolysis Bullosa

The early onset and rapid progression of cutaneous squamous cell carcinoma (cSCC) leads to high mortality rates in individuals with recessive dystrophic epidermolysis bullosa (RDEB). Currently, the molecular mechanisms underlying cSCC development in RDEB are not well understood and there are limited therapeutic options. RDEB-cSCC arises through the accumulation of genetic mutations; however, previous work analyzing gene expression profiles have not been able to explain its aggressive nature. Therefore, we generated a model to study RDEB-cSCC development using cellular reprograming and re-differentiation technology. We compared RDEB-cSCC to cSCC that were first reprogrammed into induced pluripotent stem cells (RDEB-cSCC-iPSC) and then differentiated back to keratinocytes (RDEB-cSCC-iKC). The RDEB-cSCC-iKC cell population had reduced proliferative capacities in vitro and in vivo, suggesting that reprogramming and re-differentiation leads to functional changes. Finally, we performed RNA-seq analysis for RDEB-cSCC, RDEB-cSCC-iPSC, and RDEB-cSCC-iKC and identified different gene expression signatures between these cell populations. Taken together, this cell culture model offers a valuable tool to study cSCC and provides a novel way to identify potential therapeutic targets for RDEB-cSCC.

scholarly journals Gene Expression Profiling Of Perineural Invasion In Head And Neck Cutaneous Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Timothy J. Eviston ◽  
Elahe Minaei ◽  
Simon A. Mueller ◽  
Navid Ahmadi ◽  
Bruce Ashford ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Expression Analysis ◽  
Squamous Cell ◽  
Perineural Invasion ◽  
Expression Profiles ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Mesenchymal Transition

Abstract Perineural invasion (PNI) is frequently associated with aggressive clinical behaviour in head and neck cutaneous squamous cell carcinoma (HNcSCC) leading to local recurrence and treatment failure. This study evaluates the gene expression profiles of HNcSCC with PNI using a differential expression analysis approach and constructs a tailored gene panel for sensitivity and specificity analysis. 45 cases of HNcSCC were stratified into three groups (Extensive, Focal and Non PNI) based on predefined clinicopathological criteria. Here we show HNcSCC with extensive PNI demonstrates significant up- and down-regulation of 144 genes associated with extracellular matrix interactions, epithelial to mesenchymal transition, cell adhesion, cellular motility, angiogenesis, and cellular differentiation. Gene expression of focal and non PNI cohorts were indistinguishable and were combined for further analyses. There is clinicopathological correlation between gene expression analysis findings and disease behaviour and a tailored panel of 10 genes was able to identify extensive PNI with 96% sensitivity and 95% specificity.

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