Elana Fertig

Loss of Trop2 causes ErbB3 activation through a neuregulin-1-dependent mechanism in the mesenchym... more Loss of Trop2 causes ErbB3 activation through a neuregulin-1-dependent mechanism in the mesenchymal subtype of HNSCC." Oncotarget.5,19. 9281-94. (2014).

downloadDownload free PDF

Epigenetic screening of salivary gland mucoepidermoid carcinoma identifies hypomethylation of CLIC3 as a common alteration

Oral oncology, Jan 17, 2015

The role of promoter methylation in the development of mucoepidermoid carcinoma (MEC) has not bee... more The role of promoter methylation in the development of mucoepidermoid carcinoma (MEC) has not been fully explored. In this study, we investigated the epigenetic landscape of MEC. The Illumina HumanMethylation27 BeadChip array and differential methylation analysis were utilized to screen for epigenetic alterations in 14 primary MEC tumors and 14 matched normal samples. Bisulfite sequencing was used to validate these results, with subsequent quantitative Methylation-Specific PCR (qMSP) to validate chloride intracellular channel protein 3 (CLIC3) in a separate cohort. Furthermore, CLIC3 immunohistochemical (IHC) staining was performed in another separate cohort of MEC. Finally, clinical and pathological characteristics were statistically analyzed for correlation with methylation status of CLIC3 and CLIC3 IHC H-scores by Wilcoxon rank sum, Kruskall-Wallis, and X(2) test tests. We obtained 6 significantly differentially methylated gene candidates demonstrating significant promoter hyper-...

Abstract 4807: Discovery of novel alternative splicing events in human papillomavirus-related oropharyngeal squamous cell carcinoma

Cancer Research, 2015

Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA

Nature communications, 2015

Lungs resected for adenocarcinomas often harbour minute discrete foci of cytologically atypical p... more Lungs resected for adenocarcinomas often harbour minute discrete foci of cytologically atypical pneumocyte proliferations designated as atypical adenomatous hyperplasia (AAH). Evidence suggests that AAH represents an initial step in the progression to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and fully invasive adenocarcinoma. Despite efforts to identify predictive markers of malignant transformation, alterations driving this progression are poorly understood. Here we perform targeted next-generation sequencing on multifocal AAHs and different zones of histologic progression within AISs and MIAs. Multiregion sequencing demonstrated different genetic drivers within the same tumour and reveal that clonal expansion is an early event of tumorigenesis. We find that KRAS, TP53 and EGFR mutations are indicators of malignant transition. Utilizing droplet digital PCR, we find alterations associated with early neoplasms in paired circulating DNA. This study provide...

Inferring Coordinated Gene Activity in Pattern Sets

Background / Purpose: Coordinated changes in gene expression across samples result from the under... more Background / Purpose: Coordinated changes in gene expression across samples result from the underlying biological processes distinguishing those samples. Whereas many microarray analysis techniques infer independent patterns across samples, concurrent biological processes often regulate overlapping sets of genes. Main conclusion: We present an analysis technique, Coordinated Gene Activity in Pattern Sets (CoGAPS), which infers overlapping patterns in gene expression across samples and links these patterns to activity determined through gene set analysis. For example, CoGAPS inferred expected reduction in KIT pathway activity and an unexpected DNA damage response arising from imatinib treatment of gastrointestinal tumor cell lines.

Analysis of gene expression of secreted factors associated with breast cancer metastases in breast cancer subtypes

Scientific Reports, 2015

Breast cancer is a heterogeneous disease, having multiple subtypes with different malignant pheno... more Breast cancer is a heterogeneous disease, having multiple subtypes with different malignant phenotypes. The triple-negative breast cancer, or basal breast cancer, is highly aggressive, metastatic, and difficult to treat. Previously, we identified that key molecules (IL6, CSF2, CCL5, VEGFA, and VEGFC) secreted by tumor cells and stromal cells in basal breast cancer can promote metastasis. It remains to assess whether these molecules function similarly in other subtypes of breast cancer. Here, we characterize the relative gene expression of the five secreted molecules and their associated receptors (GP130, GMRA, GMRB, CCR5, VEGFR2, NRP1, VEGFR3, NRP2) in the basal, HER2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B subtypes using high throughput data from tumor samples in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). IL6 and CCL5 gene expression are basal breast cancer specific, whereas high gene expression of GP130 was observed in luminal A/B. VEGFA/C and CSF2 mRNA are overexpressed in HER2 positive breast cancer, with VEGFA and CSF2 also overexpressed in basal breast cancer. Further study of the specific protein function of these factors within their associated cancer subtypes may yield personalized biomarkers and treatment modalities.

Abstract 527: Analysis of the interaction between microRNAs and Notch pathway members in HNSCC (head and neck squamous cell carcinoma)

Cancer Research, 2014

Abstract LB-317: Interactive pipeline for reproducible genomics analyses

Cancer Research, 2014

Decreased SMAD4 expression is associated with induction of epithelial-to-mesenchymal transition and cetuximab resistance in head and neck squamous cell carcinoma

Cancer Biology & Therapy, 2015

Epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cel... more Epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and cetuximab, a monoclonal antibody targeting this receptor, is widely used to treat these patients. In the following investigation, we examined the role of SMAD4 down-regulation in mediating epithelial-to-mesenchymal transition (EMT) and cetuximab resistance in HNSCC. We determined that SMAD4 down-regulation was significantly associated with increased cell motility, increased expression of vimentin, and cetuximab resistance in HNSCC cell lines. In the HNSCC genomic dataset obtained from The Cancer Genome Atlas, SMAD4 was altered in 20/279 (7%) of HNSCC via homozygous deletion, and nonsense, missense, and silent mutations. When SMAD4 expression was compared with respect to human papillomavirus (HPV) status, HPV-positive tumors had higher expression compared to HPV-negative tumors. Furthermore, higher SMAD4 expression also correlated with higher CDKN2A (p16) expression. Our data suggest that SMAD4 down-regulation plays an important role in the induction of EMT and cetuximab resistance. Patients with higher SMAD4 expression may benefit from cetuximab use in the clinic.

Abstract 5342: Hardwiring mechanism into predicting cancer phenotypes by computational learning

Cancer Research, 2014

Abstract 2482: Key tumor suppressor genes inactivated by promoter methylation and somatic mutations in head and neck cancer

Cancer Research, 2014

Abstract 3409: Transcription factor signature of head and neck squamous cell carcinoma

Cancer Research, 2014

Abstract 3100: MicroRNA profiling reveals miR-205 upregulation is associated with head and neck squamous cell carcinoma and modulates E2F1 signaling

Cancer Research, 2013

Abstract 2474: Smad4 loss induces cetuximab resistance and increased metastatic potential in head and neck squamous cell carcinoma

Cancer Research, 2014

Abstract B45: The Twist box domain is required for Twist1-induced metastasis of prostate cancer cells

by Jessica Cades, Russell Williams, and Elana Fertig

Cancer Research, 2013

NF-κB and STAT3 transcription factor signatures differentiate HPV-positive and HPV-negative Head and neck squamous cell carcinoma

International journal of cancer. Journal international du cancer, Jan 9, 2015

Using high-throughput analyses and the TRANSFAC database, we characterized TF signatures of head ... more Using high-throughput analyses and the TRANSFAC database, we characterized TF signatures of head and neck squamous cell carcinoma (HNSCC) subgroups by inferential analysis of target gene expression, correcting for the effects of DNA methylation and copy number. Using this discovery pipeline, we determined that human papillomavirus-related (HPV+) and HPV- HNSCC differed significantly based on the activity levels of key TFs including AP1, STATs, NF-κB, and p53. Immunohistochemical analysis confirmed that HPV- HNSCC is characterized by co-activated STAT3 and NF-κB pathways, and functional studies demonstrate that this phenotype can be effectively targeted with combined anti-NF-κB and anti-STAT therapies. These discoveries correlate strongly with previous findings connecting STATs, NF-κB, and AP1 in HNSCC. We identified 5 top-scoring pair biomarkers from STATs, NF-κB and AP1 pathways that distinguish HPV+ from HPV- HNSCC based on TF activity, and validated these biomarkers on TCGA and o...

Abstract 2901: An integrated matrix factorization algorithm for DNA methylation and gene expression identi es HNSCC clinical subtypes and GLI1 signaling speci c to HPV-negative HNSCC

by D. Gaykalova and Elana Fertig

Cancer Research, 2013

Loss of Trop2 causes ErbB3 activation through a neuregulin-1-dependent mechanism in the mesenchymal subtype of HNSCC

Oncotarget, Jan 15, 2014

In head and neck squamous cell cancer (HNSCC), four intrinsic subtypes (or groups) have been iden... more In head and neck squamous cell cancer (HNSCC), four intrinsic subtypes (or groups) have been identified, and each one possesses a unique biology that will require specific treatment strategies. We previously reported that mesenchymal (group 2) tumors exhibit reduced levels of Trop2 expression. In this study, we investigated the functional role of Trop2 in HNSCC and find that loss results in autocrine activation of the EGFR family member ErbB3 via neuregulin-1. Trop2 localizes to both the cell surface and cytosol of HNSCC cells and forms a complex with neuregulin-1, which is predominantly cytosolic. Inactivation of Trop2 increases the concentration of neuregulin-1 at the cell surface where it is cleaved to activate ErbB3. In primary HNSCC, detection of ErbB3 activation was limited to Trop2 negative tumors. An analysis of the Cancer Genome Atlas (TCGA) HNSCC dataset confirms enrichment for ErbB3 activity in mesenchymal tumors. Notably, Trop2 loss triggers sensitivity to anti-ErbB3 ant...

downloadDownload free PDF

AGA: Interactive pipeline for reproducible genomics analyses

F1000Research, 2015

Automated Genomics Analysis (AGA) is an interactive program to analyze high-throughput genomic da... more Automated Genomics Analysis (AGA) is an interactive program to analyze high-throughput genomic data sets on a variety of platforms. An easy to use, point and click, guided pipeline is implemented to combine, define, and compare datasets, and customize their outputs. In contrast to other automated programs, AGA enables flexible selection of sample groups for comparison from complex sample annotations. Batch correction techniques are also included to further enable the combination of datasets from diverse studies in this comparison. AGA also allows users to save plots, tables and data, and log files containing key portions of the R script run for reproducible analyses. The link between the interface and R supports collaborative research, enabling advanced R users to extend preliminary analyses generated from bioinformatics novices.

P16 Protein Expression and Human Papillomavirus Status as Prognostic Biomarkers of Nonoropharyngeal Head and Neck Squamous Cell Carcinoma

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 10, 2014

Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infec... more Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx. p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics. p16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 ...

Before you go

Make your research this easy to find.

Create your free profile

Elana Fertig

Uploads

Papers by Elana Fertig

Log In