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https://www.readbyqxmd.com/read/28314692/identification-of-an-atypical-etiological-head-and-neck-squamous-carcinoma-subtype-featuring-the-cpg-island-methylator-phenotype
#1
K Brennan, J L Koenig, A J Gentles, J B Sunwoo, O Gevaert
Head and neck squamous cell carcinoma (HNSCC) is broadly classified into HNSCC associated with human papilloma virus (HPV) infection, and HPV negative HNSCC, which is typically smoking-related. A subset of HPV negative HNSCCs occur in patients without smoking history, however, and these etiologically 'atypical' HNSCCs disproportionately occur in the oral cavity, and in female patients, suggesting a distinct etiology. To investigate the determinants of clinical and molecular heterogeneity, we performed unsupervised clustering to classify 528 HNSCC patients from The Cancer Genome Atlas (TCGA) into putative intrinsic subtypes based on their profiles of epigenetically (DNA methylation) deregulated genes...
March 1, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28255813/gene-promoter-associated-cpg-island-hypermethylation-in-squamous-cell-carcinoma-of-the-tongue
#2
Samatha Bhat, Shama Prasada Kabekkodu, Chinchu Jayaprakash, Raghu Radhakrishnan, Satadru Ray, Kapaettu Satyamoorthy
The present study was undertaken to explore and validate novel hypermethylated DNA regions in squamous cell carcinoma of the tongue (SCCT). Genome-wide methylation changes were identified by differential methylation hybridization (DMH) microarray and validated by bisulfite genome sequencing (BGS). The results were compared against datasets from The Cancer Genome Atlas head and neck squamous cell carcinoma (TCGA-HNSCC), Gene Expression Omnibus (GSE26549), and ArrayExpress (E-MTAB-1328). DMH identified 116 hypomethylated and 241 hypermethylated regions...
March 2, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28174608/genome-wide-dna-methylation-profile-identified-a-unique-set-of-differentially-methylated-immune-genes-in-oral-squamous-cell-carcinoma-patients-in-india
#3
Baidehi Basu, Joyeeta Chakraborty, Aditi Chandra, Atul Katarkar, Jadav Ritesh Kumar Baldevbhai, Debjit Dhar Chowdhury, Jay Gopal Ray, Keya Chaudhuri, Raghunath Chatterjee
BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the common malignancies in Southeast Asia. Epigenetic changes, mainly the altered DNA methylation, have been implicated in many cancers. Considering the varied environmental and genotoxic exposures among the Indian population, we conducted a genome-wide DNA methylation study on paired tumor and adjacent normal tissues of ten well-differentiated OSCC patients and validated in an additional 53 well-differentiated OSCC and adjacent normal samples...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28174607/pitx3-dna-methylation-is-an-independent-predictor-of-overall-survival-in-patients-with-head-and-neck-squamous-cell-carcinoma
#4
Verena Sailer, Emily Eva Holmes, Heidrun Gevensleben, Diane Goltz, Freya Dröge, Alina Franzen, Jörn Dietrich, Glen Kristiansen, Friedrich Bootz, Andreas Schröck, Dimo Dietrich
BACKGROUND: Molecular biomarkers assisting risk-group assignment and subsequent treatment stratification are urgently needed for patients with squamous cell cancer of the head and neck region (HNSCC). Aberrant methylation is a frequent event in cancer and, therefore, a promising source for potential biomarkers. Here, the methylation status of the paired-like homeodomain transcription factor 3 (PITX3) was evaluated in HNSCC. METHODS: Using a quantitative real-time PCR, PITX3 methylation was assessed in a cohort of 326 HNSCC patients treated for localized or locally advanced disease (training cohort)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28146432/integrative-computational-analysis-of-transcriptional-and-epigenetic-alterations-implicates-dtx1-as-a-putative-tumor-suppressor-gene-in-hnscc
#5
Daria A Gaykalova, Veronika Zizkova, Theresa Guo, Ilse Tiscareno, Yingying Wei, Rajita Vatapalli, Patrick T Hennessey, Julie Ahn, Ludmila Danilova, Zubair Khan, Justin A Bishop, J Silvio Gutkind, Wayne M Koch, William H Westra, Elana J Fertig, Michael F Ochs, Joseph A Califano
Over a half million new cases of Head and Neck Squamous Cell Carcinoma (HNSCC) are diagnosed annually worldwide, however, 5 year overall survival is only 50% for HNSCC patients. Recently, high throughput technologies have accelerated the genome-wide characterization of HNSCC. However, comprehensive pipelines with statistical algorithms that account for HNSCC biology and perform independent confirmatory and functional validation of candidates are needed to identify the most biologically relevant genes. We applied outlier statistics to high throughput gene expression data, and identified 76 top-scoring candidates with significant differential expression in tumors compared to normal tissues...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28146422/mage-expression-in-head-and-neck-squamous-cell-carcinoma-primary-tumors-lymph-node-metastases-and-respective-recurrencesimplications-for-immunotherapy
#6
Simon Laban, Gregor Giebel, Niklas Klümper, Andreas Schröck, Johannes Doescher, Giulio Spagnoli, Julia Thierauf, Marie-Nicole Theodoraki, Romain Remark, Sacha Gnjatic, Rosemarie Krupar, Andrew G Sikora, Geert Litjens, Niels Grabe, Glen Kristiansen, Friedrich Bootz, Patrick J Schuler, Cornelia Brunner, Johannes Brägelmann, Thomas K Hoffmann, Sven Perner
Melanoma associated antigens (MAGE) are potential targets for immunotherapy and have been associated with poor overall survival (OS) in head and neck squamous cell carcinoma (HNSCC). However, little is known about MAGE in lymph node metastases (LNM) and recurrent disease (RD) of HNSCC.To assess whether MAGE expression increases with metastasis or recurrence, a tissue microarray (TMA) of 552 primary tumors (PT), 219 LNM and 75 RD was evaluated by immunohistochemistry for MAGE antigens using three monoclonal antibodies to multiple MAGE family members...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28109471/smoking-status-regulates-a-novel-panel-of-piwi-interacting-rnas-in-head-and-neck-squamous-cell-carcinoma
#7
Aswini R Krishnan, Avinaash Korrapati, Angela E Zou, Yuanhao Qu, Xiao Qi Wang, Joseph A Califano, Jessica Wang-Rodriguez, Scott M Lippman, Melbourne F Hovell, Weg M Ongkeko
OBJECTIVE: Smoking remains a primary etiological factor in head and neck squamous cell carcinoma (HNSCC). Given that non-coding RNAs (ncRNAs), including PIWI-interacting RNAs (piRNAs), have emerged as mediators of initiation and progression in head and neck malignancies, we undertook a global study of piRNA expression patterns in smoking-associated HNSCC. MATERIALS AND METHODS: Using RNA-sequencing data from 256 current smoker and lifelong nonsmoker samples in The Cancer Genome Atlas (TCGA), we analyzed the differential expression patterns of 27,127 piRNAs across patient cohorts stratified by tobacco use, with HPV16 status and tumor status taken into account...
February 2017: Oral Oncology
https://www.readbyqxmd.com/read/28039268/therapeutic-small-molecules-target-inhibitor-of-apoptosis-proteins-in-cancers-with-deregulation-of-extrinsic-and-intrinsic-cell-death-pathways
#8
REVIEW
Adeeb Derakhshan, Zhong Chen, Carter Van Waes
The Cancer Genome Atlas (TCGA) has unveiled genomic deregulation of various components of the extrinsic and intrinsic apoptotic pathways in different types of cancers. Such alterations are particularly common in head and neck squamous cell carcinomas (HNSCC), which frequently display amplification and overexpression of the Fas-associated via death domain (FADD) and inhibitor of apoptosis proteins (IAP) that complex with members of the TNF receptor family. Second mitochondria-derived activator of caspases (SMAC) mimetics, modeled after the endogenous IAP antagonist SMAC, and IAP inhibitors represent important classes of novel small molecules currently in phase I/II clinical trials...
March 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27867017/genomic-amplification-of-fanconi-anemia-complementation-group-a-fanca-in-head-and-neck-squamous-cell-carcinoma-hnscc-cellular-mechanisms-of-radioresistance-and-clinical-relevance
#9
Julia Hess, Kristian Unger, Michael Orth, Ulrike Schötz, Lars Schüttrumpf, Verena Zangen, Igor Gimenez-Aznar, Agata Michna, Ludmila Schneider, Ramona Stamp, Martin Selmansberger, Herbert Braselmann, Ludwig Hieber, Guido A Drexler, Sebastian Kuger, Diana Klein, Verena Jendrossek, Anna A Friedl, Claus Belka, Horst Zitzelsberger, Kirsten Lauber
Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27859938/head-and-neck-squamous-cell-carcinoma-ambiguous-human-papillomavirus-status-elevated-p16-and-deleted-retinoblastoma-1
#10
Tim N Beck, Chad H Smith, Douglas B Flieder, Thomas J Galloway, John A Ridge, Erica A Golemis, Ranee Mehra
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is potentially curable, but treatment planning remains a challenge. Oncogenic human papillomavirus (HPV)-positive disease is often associated with a good prognosis compared with HPV-negative disease. However, some HPV-positive HNSCC recurs, often with distant metastases and significant treatment resistance. METHODS AND RESULTS: We performed p16 immunohistochemistry (IHC), in situ hybridization (ISH) for high-risk HPV, and comprehensive genomic profiling on oropharyngeal HNSCC with basaloid features and particularly aggressive disease course, noting a rare genetic event: a deleting mutation (exons 5-17) of the tumor suppressor and dominant cell cycle regulator retinoblastoma 1 (RB1)...
March 2017: Head & Neck
https://www.readbyqxmd.com/read/27855189/genomic-and-transcriptomic-alterations-associated-with-stat3-activation-in-head-and-neck-cancer
#11
Noah D Peyser, Kelsey Pendleton, William E Gooding, Vivian W Y Lui, Daniel E Johnson, Jennifer R Grandis
BACKGROUND: Hyperactivation of STAT3 via constitutive phosphorylation of tyrosine 705 (Y705) is common in most human cancers, including head and neck squamous carcinoma (HNSCC). STAT3 is rarely mutated in cancer and the (epi)genetic alterations that lead to STAT3 activation are incompletely understood. Here we used an unbiased approach to identify genomic and epigenomic changes associated with pSTAT3(Y705) expression using data generated by The Cancer Genome Atlas (TCGA). METHODS AND FINDINGS: Mutation, mRNA expression, promoter methylation, and copy number alteration data were extracted from TCGA and examined in the context of pSTAT3(Y705) protein expression...
2016: PloS One
https://www.readbyqxmd.com/read/27777979/the-head-and-neck-cancer-immune-landscape-and-its-immunotherapeutic-implications
#12
Rajarsi Mandal, Yasin Şenbabaoğlu, Alexis Desrichard, Jonathan J Havel, Martin G Dalin, Nadeem Riaz, Ken-Wing Lee, Ian Ganly, A Ari Hakimi, Timothy A Chan, Luc G T Morris
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27669890/epidermal-growth-factor-egf-receptor-ligand-based-molecular-staging-predicts-prognosis-in-head-and-neck-squamous-cell-carcinoma-partly-due-to-deregulated-egf-induced-amphiregulin-expression
#13
Jian Gao, Camilla H Ulekleiv, Trond S Halstensen
BACKGROUND: Increased expression of epidermal growth factor receptor (EGFR) and its ligands is associated with poor prognosis and chemoresistance in many carcinoma types, but its role in head and neck squamous cell carcinoma (HNSCC) is unclear. Our aim was to clarify whether mRNA expression of EGFR-ligands was linked to prognosis and cisplatin resistance, and if so, which ligand was most important and how was the expression regulated. METHODS: To examine the prognostic effect of EGFR-ligand expression, we analyzed tumorous mRNA expression in 399 HNSCC patients...
September 26, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27658780/hox-genes-potential-candidates-for-the-progression-of-laryngeal-squamous-cell-carcinoma
#14
Rafaela de Barros E Lima Bueno, Anelisa Ramão, Daniel Guariz Pinheiro, Cleidson Padua Alves, Vinicius Kannen, Achim A Jungbluth, Luiza Ferreira de Araújo, Bruna Rodrigues Muys, Aline Simoneti Fonseca, Jessica Rodrigues Plaça, Rodrigo Alexandre Panepucci, Luciano Neder, Fabiano P Saggioro, Rui Celso M Mamede, David Livingstone Alves Figueiredo, Wilson Araújo Silva
Laryngeal squamous cell carcinoma (LSCC) is a very aggressive cancer, considered to be a subtype of the head and neck squamous cell carcinoma (HNSCC). Despite significant advances in the understanding and treatment of cancer, prognosis of patients with LSCC has not improved recently. In the present study, we sought to understand better the genetic mechanisms underlying LSCC development. Thirty-two tumor samples were collected from patients undergoing surgical resection of LSCC. The samples were submitted to whole-genome cDNA microarray analysis aiming to identify genetic targets in LSCC...
November 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27650546/cogaps-matrix-factorization-algorithm-identifies-transcriptional-changes-in-ap-2alpha-target-genes-in-feedback-from-therapeutic-inhibition-of-the-egfr-network
#15
Elana J Fertig, Hiroyuki Ozawa, Manjusha Thakar, Jason D Howard, Luciane T Kagohara, Gabriel Krigsfeld, Ruchira S Ranaweera, Robert M Hughes, Jimena Perez, Siân Jones, Alexander V Favorov, Jacob Carey, Genevieve Stein-O'Brien, Daria A Gaykalova, Michael F Ochs, Christine H Chung
Patients with oncogene driven tumors are treated with targeted therapeutics including EGFR inhibitors. Genomic data from The Cancer Genome Atlas (TCGA) demonstrates molecular alterations to EGFR, MAPK, and PI3K pathways in previously untreated tumors. Therefore, this study uses bioinformatics algorithms to delineate interactions resulting from EGFR inhibitor use in cancer cells with these genetic alterations. We modify the HaCaT keratinocyte cell line model to simulate cancer cells with constitutive activation of EGFR, HRAS, and PI3K in a controlled genetic background...
September 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27649287/ephrin-b2-overexpression-predicts-for-poor-prognosis-and-response-to-therapy-in-solid-tumors
#16
Ayman Oweida, Shilpa Bhatia, Kellen Hirsch, Dylan Calame, Anastacia Griego, Steve Keysar, Todd Pitts, Jaspreet Sharma, Gail Eckhardt, Antonio Jimeno, Xiao Jing Wang, Gill Parkash, Joseph Califano, Sana D Karam
Ephrin B2 is variably expressed on tumor cells and its blockade has been shown to inhibit angiogenesis in animal models of pancreatic, colorectal, lung and head, and neck squamous cell carcinomas. However, the implications of ephrinB2 expression in cancer patients have remained elusive. In this study, we analyzed the cancer genome atlas (TCGA) for ephrinB2 expression. We report significant correlations between EFNB2 expression, overall survival and disease-free survival in head and neck squamous cell carcinoma (HNSCC, n = 519), pancreatic adenocarcinoma (n = 186), and bladder urothelial carcinoma (n = 410)...
March 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27603913/cancer-testis-antigens-expression-regulation-tumor-invasion-and-use-in-immunotherapy-of-cancers
#17
REVIEW
Arash Salmaninejad, Mohammad Reza Zamani, Mehrnaz Pourvahedi, Zahra Golchehre, Ali Hosseini Bereshneh, Nima Rezaei
UNLABELLED: Cancer/testis antigens (CTAs) are named based on their expression pattern that is restricted in a number of normal and abnormal tissues. Tumor cells frequently express antigens whose expression is typically restricted to germ cells. Their unique expression pattern is guaranteed by precise epigenetic regulatory mechanisms. Because of their tumor-limited, high immunogenicity, and biased expression, discovery of these molecules provides unprecedented opportunities for further research and clinical development in the field of cancer diagnosis and immunotherapy...
October 2016: Immunological Investigations
https://www.readbyqxmd.com/read/27601166/lower-dsc1-expression-is-related-to-the-poor-differentiation-and-prognosis-of-head-and-neck-squamous-cell-carcinoma-hnscc
#18
Yating Wang, Chen Chen, Xiaofei Wang, Fengtong Jin, Yan Liu, Huiqiao Liu, Ting Li, Jiangtao Fu
PURPOSE: Although desmocollins have an important position in cancer-related research, there are little reports about the relations between cancers and desmocollin 1 (DSC1). The present study was designed to investigate the correlations between DSC1 and head and neck squamous cell carcinoma (HNSCC). METHODS: First we analyzed the GEO database; then, HNSCC and pericarcinous tissues were collected to verify the results. DSC1 expression was detected by western blot and real-time PCR...
December 2016: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27596625/mutational-load-and-mutational-patterns-in-relation-to-age-in-head-and-neck-cancer
#19
Stefano Meucci, Ulrich Keilholz, Ingeborg Tinhofer, Oliva A Ebner
Head and neck squamous cell carcinoma (HNSCC) is a cancer with well-defined tumor causes such as HPV infection, smoking and drinking. Using The Cancer Genome Atlas (TCGA) HNSCC cohort we systematically studied the mutational load as well as patterns related to patient age in HNSCC. To obtain a homogenous set we excluded all patients with HPV infection as well as wild type TP53. We found that the overall mutational load is higher in patients of old age. Through unsupervised hierarchical clustering, we detected distinct mutational clusters in very young as well as very old patients...
August 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27507850/egfr-and-rb1-as-dual-biomarkers-in-hpv-negative-head-and-neck-cancer
#20
Tim N Beck, Rachel Georgopoulos, Elena I Shagisultanova, David Sarcu, Elizabeth A Handorf, Cara Dubyk, Miriam N Lango, John A Ridge, Igor Astsaturov, Ilya G Serebriiskii, Barbara A Burtness, Ranee Mehra, Erica A Golemis
Clinical decision making for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is predominantly guided by disease stage and anatomic location, with few validated biomarkers. The epidermal growth factor receptor (EGFR) is an important therapeutic target, but its value in guiding therapeutic decision making remains ambiguous. We integrated analysis of clinically annotated tissue microarrays with analysis of data available through the TCGA, to investigate the idea that expression signatures involving EGFR, proteins regulating EGFR function, and core cell-cycle modulators might serve as prognostic or drug response-predictive biomarkers...
October 2016: Molecular Cancer Therapeutics
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