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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 (IAPs), that complex with members of the tumor necrosis factor (TNF) receptor family. SMAC mimetics, modeled after the endogenous IAP antagonist second mitochondria-derived activator of caspases (SMAC), and IAP inhibitors, represent important classes of novel small-molecules currently in phase I/II clinical trials...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
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)...
November 8, 2016: Head & Neck
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
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
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
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
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
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 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)...
September 20, 2016: Molecular Carcinogenesis
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
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
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
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
Danielle F Eytan, Grace E Snow, Sophie Carlson, Adeeb Derakhshan, Anthony Saleh, Stephen Schiltz, Hui Cheng, Suresh Mohan, Shaleeka Cornelius, Jamie Coupar, Anastasia L Sowers, Lidia Hernandez, James B Mitchell, Christina M Annunziata, Zhong Chen, Carter Van Waes
Comparison of tumors from The Cancer Genome Atlas (TCGA) reveals that head and neck squamous cell carcinomas (HNSCC) harbor the most frequent genomic amplifications of Fas-associated death domain (FADD), with or without Baculovirus inhibitor of apoptosis repeat containing BIRC2 (cIAP1), affecting about 30% of patients in association with worse prognosis. Here, we identified HNSCC cell lines harboring FADD/BIRC2 amplifications and overexpression by exome sequencing, RT-PCR, and Western blotting. In vitro, FADD or BIRC2 siRNA knockdown inhibited HNSCC displaying amplification and increased expression of these genes, supporting their functional importance in promoting proliferation...
September 15, 2016: Cancer Research
Oliver Wood, Jeongmin Woo, Gregory Seumois, Natalia Savelyeva, Katy J McCann, Divya Singh, Terry Jones, Lailah Peel, Michael S Breen, Matthew Ward, Eva Garrido Martin, Tilman Sanchez-Elsner, Gareth Thomas, Pandurangan Vijayanand, Christopher H Woelk, Emma King, Christian Ottensmeier
Human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than it's HPV negative (HPV(-)) counterpart. This may be due to the higher numbers of tumor-infiltrating lymphocytes (TILs) in HPV positive (HPV(+)) tumors. RNA-Sequencing (RNA-Seq) was used to evaluate whether the differences in clinical behaviour simply reflect a numerical difference in TILs or whether there is a fundamental behavioural difference between TILs in these two settings. Thirty-nine HNSCC tumors were scored for TIL density by immunohistochemistry...
August 30, 2016: Oncotarget
Annette M Lim, Nicholas C Wong, Ruth Pidsley, Elena Zotenko, June Corry, Alexander Dobrovic, Susan J Clark, Danny Rischin, Benjamin Solomon
BACKGROUND: DNA methylation profiling of heterogeneous head and neck squamous cell carcinoma (HNSCC) cohorts has been reported to predict patient outcome. We investigated if a prognostic DNA methylation profile could be found in tumour tissue from a single uniform subsite, the oral tongue. The methylation status of 109 comprehensively annotated oral tongue squamous cell carcinoma (OTSCC) formalin-fixed paraffin-embedded (FFPE) samples from a single institution were examined with the Illumina HumanMethylation450K (HM450K) array...
2016: Clinical Epigenetics
Nijiro Nohata, Martin C Abba, J Silvio Gutkind
OBJECTIVES: The role of long non-coding RNA (lncRNA) expression in human head and neck squamous cell carcinoma (HNSCC) is still poorly understood. In this study, we aimed at establishing the onco-lncRNAome profiling of HNSCC and to identify lncRNAs correlating with prognosis and patient survival. MATERIALS AND METHODS: The Atlas of Noncoding RNAs in Cancer (TANRIC) database was employed to retrieve the lncRNA expression information generated from The Cancer Genome Atlas (TCGA) HNSCC RNA-sequencing data...
August 2016: Oral Oncology
Pawan Upadhyay, Sudhir Nair, Ekjot Kaur, Jyotirmoi Aich, Prachi Dani, Vidyalakshmi Sethunath, Nilesh Gardi, Pratik Chandrani, Mukul Godbole, Kavita Sonawane, Ratnam Prasad, Sadhana Kannan, Beamon Agarwal, Shubhada Kane, Sudeep Gupta, Shilpee Dutt, Amit Dutt
BACKGROUND: Notch pathway plays a complex role depending on cellular contexts: promotes stem cell maintenance or induces terminal differentiation in potential cancer-initiating cells; acts as an oncogene in lymphocytes and mammary tissue or plays a growth-suppressive role in leukemia, liver, skin, and head and neck cancer. Here, we present a novel clinical and functional significance of NOTCH1 alterations in early stage tongue squamous cell carcinoma (TSCC). PATIENTS AND METHODS: We analyzed the Notch signaling pathway in 68 early stage TSCC primary tumor samples by whole exome and transcriptome sequencing, real-time PCR based copy number, expression, immuno-histochemical, followed by cell based biochemical and functional assays...
August 2, 2016: Oncotarget
Alice N Weaver, M Benjamin Burch, Tiffiny S Cooper, Deborah L Della Manna, Shi Wei, Akinyemi I Ojesina, Eben L Rosenthal, Eddy S Yang
UNLABELLED: Oral squamous cell carcinoma (OSCC) is a cancer subtype that lacks validated prognostic and therapeutic biomarkers, and human papillomavirus status has not proven beneficial in predicting patient outcomes. A gene expression pathway analysis was conducted using OSCC patient specimens to identify molecular targets that may improve management of this disease. RNA was isolated from 19 OSCCs treated surgically at the University of Alabama at Birmingham (UAB; Birmingham, AL) and evaluated using the NanoString nCounter system...
September 2016: Molecular Cancer Research: MCR
Angela E Zou, Hao Zheng, Maarouf A Saad, Mehran Rahimy, Jonjei Ku, Selena Z Kuo, Thomas K Honda, Jessica Wang-Rodriguez, Yinan Xuan, Avinaash Korrapati, Vicky Yu, Pranav Singh, Jennifer R Grandis, Charles C King, Scott M Lippman, Xiao Qi Wang, Andrew Hinton, Weg M Ongkeko
Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease marked by frequent recurrence and metastasis and stagnant survival rates. To enhance molecular knowledge of HNSCC and define a non-coding RNA (ncRNA) landscape of the disease, we profiled the transcriptome-wide dysregulation of long non-coding RNA (lncRNA), microRNA (miRNA), and PIWI-interacting RNA (piRNA) using RNA-sequencing data from 422 HNSCC patients in The Cancer Genome Atlas (TCGA). 307 non-coding transcripts differentially expressed in HNSCC were significantly correlated with patient survival, and associated with mutations in TP53, CDKN2A, CASP8, PRDM9, and FBXW7 and copy number variations in chromosomes 3, 5, 7, and 18...
9, 2016: Oncotarget
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