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Head and neck cancer genetics

Andrew P Zammit, Rohit Sinha, Caroline L Cooper, Christopher F L Perry, Ian H Frazer, Zewen K Tuong
Oral cavity Squamous Cell Carcinoma (OCSCC) is a common form of head and neck cancer throughout the developed and developing world. However, the etiology of OCSCC is still unclear. Here, we explored the extent to which tobacco use, Human Papillomavirus (HPV) infection and genetic and transcriptomic changes contributed to the oncogenesis of OCSCC. In a prospective observational study, we analysed fresh tissue biopsies from 45 OCSCC collected from 51 subjects presenting with OCSCC to the Brisbane Head and Neck Clinics between 2013 and 2015...
2018: PloS One
Jiao Yuan, Zhongyi Hu, Brandon A Mahal, Sihai D Zhao, Kevin H Kensler, Jingjiang Pi, Xiaowen Hu, Youyou Zhang, Yueying Wang, Junjie Jiang, Chunsheng Li, Xiaomin Zhong, Kathleen T Montone, Guoqiang Guan, Janos L Tanyi, Yi Fan, Xiaowei Xu, Mark A Morgan, Meixiao Long, Yuzhen Zhang, Rugang Zhang, Anil K Sood, Timothy R Rebbeck, Chi V Dang, Lin Zhang
Disparities in cancer care have been a long-standing challenge. We estimated the genetic ancestry of The Cancer Genome Atlas patients, and performed a pan-cancer analysis on the influence of genetic ancestry on genomic alterations. Compared with European Americans, African Americans (AA) with breast, head and neck, and endometrial cancers exhibit a higher level of chromosomal instability, while a lower level of chromosomal instability was observed in AAs with kidney cancers. The frequencies of TP53 mutations and amplification of CCNE1 were increased in AAs in the cancer types showing higher levels of chromosomal instability...
October 8, 2018: Cancer Cell
Sining Zhu, Juan Jin, Samantha Gokhale, Angeli M Lu, Haiyan Shan, Jianjun Feng, Ping Xie
The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of cytoplasmic adaptor proteins regulate the signal transduction pathways of a variety of receptors, including the TNF-R superfamily, Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and cytokine receptors. TRAF-dependent signaling pathways participate in a diverse array of important cellular processes, including the survival, proliferation, differentiation, and activation of different cell types. Many of these TRAF-dependent signaling pathways have been implicated in cancer pathogenesis...
2018: Frontiers in Immunology
Marisa C Eisenberg, Lora P Campredon, Andrew F Brouwer, Heather M Walline, Brittany M Marinelli, Yan Kwan Lau, Trey B Thomas, Rachel L Delinger, Taylor S Sullivan, Monica L Yost, Christine M Goudsmit, Thomas E Carey, Rafael Meza
INTRODUCTION: Human papillomavirus (HPV) is the primary cause of cervical and other anogenital cancers and is also associated with head and neck cancers. Incidence of HPV-related oropharyngeal squamous cell cancers (OPSCCs) is increasing, and HPV-related OPSCCs have surpassed cervical cancer as the most common HPV-related cancer in the USA. Given the multisite nature of HPV, there is strong interest in collecting data from both genital and oral sites, as well as associated data on social and sexual behaviours...
October 2, 2018: BMJ Open
Joshua E Lubek
Ongoing genetic and epigenetic research involving DNA methylation, salivary biomarkers, wild-type p53 tumor suppressor gene proteins, and HPV oncogenes are being directed at identification and treatment of dysplastic and malignant squamous cell mucosal lesions. Research is being conducted to improve immunotherapy drug response rates by increasing the amount of inflammation within the tumor microenvironment. Ongoing research is focused on the application of the antidiabetic drug metformin for the prevention and management of oral squamous cell dysplastic lesions...
November 2018: Oral and Maxillofacial Surgery Clinics of North America
Erika Tóth
Over the past decade, human papillomavirus-related oropharyngeal squamous cell carcinoma has become a distinct entity that differs from conventional head and neck cancer in many ways including its epidemiology, genetics, tumor behavior, and prognosis. Human papillomavirus-related oropharyngeal squamous cell carcinomas also exhibit characteristic histologic features. This review will cover the histomorphologic appearances of human papillomavirus-related oropharyngeal carcinoma, with an emphasis on their differences from conventional, human papillomavirus-unrelated cancer...
September 26, 2018: Magyar Onkologia
Daniela Russo, Francesco Merolla, Silvia Varricchio, Giovanni Salzano, Giovanni Zarrilli, Massimo Mascolo, Viviana Strazzullo, Rosa Maria Di Crescenzo, Angela Celetti, Gennaro Ilardi
Oral and oropharyngeal cancers represent the two most common malignancies of the head and neck region. The major risk factors for these cancers include alcohol consumption, tobacco use (via smoking or chewing) and high-risk human papillomavirus infection. The transition from normal epithelium to premalignant tissue and finally carcinoma is in part caused by a summation of genetic and epigenetic modifications. Epigenetic refers to modifications in the way the genome is expressed in cells. The most common examples of epigenetic control of gene expression are DNA methylation, histone modification and regulation by small non-coding RNAs...
October 2018: Biomedical Reports
D Vicky de Boer, Arjen Brink, Marijke Buijze, Marijke Stigter-van Walsum, Keith D Hunter, Bauke Ylstra, Elisabeth Bloemena, C René Leemans, Ruud H Brakenhoff
Head and neck squamous cell carcinomas (HNSCCs) develop in fields of genetically altered cells. These fields are often dysplastic and a subset can be recognized as (erythro)leukoplakia, but most are macroscopically invisible. There is a lack of adequate treatment options to eradicate these fields, while they underlie the development of primary tumors as well as part of the local relapses. Unfortunately, there are almost no representative cellular models available to identify suitable treatment options. To this end, clinical biopsy specimens (n=98) were cultured from normal appearing mucosa of the surgical margins of patients with primary HNSCCs (n=32) to generate precancer cell culture models...
September 17, 2018: Molecular Cancer Research: MCR
Carla Bento Nelem-Colturato, Patrícia Maluf Cury, Thiago Machado Pereira, Isabelle Silva Cosso, Kellin Pivato, Luiz Evaristo Ricci Volpato, Alvaro Henrique Borges
Background: Field cancerization is a phenomenon in which prolonged exposure to carcinogens induces changes throughout the epithelium leaving the field ready for the appearance of premalignant or malignant lesions. These alterations can promote the development of multiple carcinomas and explain the appearance of recurrences and second primary tumors. The objective of this study was to report the case of a patient who developed six oral cavity tumors in five years of treatment and, also, demonstrate the immunohistochemical changes for p53 and Ki-67, routinely used to assess dysplasic regions...
2018: Case Reports in Pathology
Kazuhiro Kobayashi, Kenji Hisamatsu, Natsuko Suzui, Akira Hara, Hiroyuki Tomita, Tatsuhiko Miyazaki
Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal lining of the upper aerodigestive tract. Tobacco and alcohol use have been reported to be associated with HNSCC. Infection with high-risk human papillomaviruses (HPVs) has recently been implicated in the pathogenesis of HNSCCs. It is now widely accepted that high-risk HPV is a cause of almost all cervical cancers as well as some forms of HNSCCs. HPV-related HNSCCs are increasing. HPV-related HNSCCs and HPV-unrelated HNSCCs differ with respect to the molecular mechanisms underlying their oncogenic processes...
August 27, 2018: Journal of Clinical Medicine
Peter W Nagle, Nynke A Hosper, Lara Barazzuol, Anne L Jellema, Mirjam Baanstra, Marc-Jan van Goethem, Sytze Brandenburg, Ulrich Giesen, Johannes A Langendijk, Peter van Luijk, Rob P Coppes
PURPOSE: Radiotherapy for head and neck cancer may result in serious side effects, such as hyposalivation, impairing the patient's quality of life. Modern radiotherapy techniques attempt to reduce the dose to salivary glands (SG), which however, results in low-dose irradiation of the tissue stem cells. Here we assess the low-dose sensitivity of tissue stem cells and the consequences for tissue function. EXPERIMENTAL DESIGN: Post-irradiation rat SG secretory function was determined after pilocarpine induction...
August 22, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yurie Mikami, Shinsuke Fujii, Ken-Ichi Kohashi, Yuichi Yamada, Masafumi Moriyama, Shintaro Kawano, Seiji Nakamura, Yoshinao Oda, Tamotsu Kiyoshima
Low-grade myofibroblastic sarcoma (LGMS) is a rare intermediate tumor, which rarely metastasizes and has myofibroblastic differentiation in various sites. It is particularly associated with the tongue in the head and neck region. The lack of any pathological features means it is difficult to make a conclusive diagnosis of LGMS. The immunohistochemical features and genomic rearrangements, including SS18-SSXs and MYH9-USP6s and the genetic mutations of cancer-associated genes, including APC, CTNNB1, EGFR, KRAS, PIK3CA and p53 were examined in a case of LGMS arising in the tip of the tongue...
September 2018: Oncology Letters
Zheng Wang, Zi-Ming Gao, Hai-Bo Huang, Li-Sha Sun, An-Qi Sun, Kai Li
Purpose: No consensus exists on the impact of polymorphisms in cytokines (such as interleukin IL-8 and IL-18) on cancer risk; moreover, there is very little evidence regarding head and neck cancer (HNC). Methods: Thus, a meta-analysis including 22 studies with 4731 cases and 8736 controls was conducted to evaluate this association. The summary odds ratio (OR) and corresponding 95% confidence intervals (CIs) for C-X-C motif chemokine ligand 8 (CXCL8, which encodes IL-8) and IL-18 polymorphisms and HNC risk were estimated...
2018: Cancer Management and Research
Vladimir Vukovic, Jovana Stojanovic, Alessia Vecchioni, Roberta Pastorino, Stefania Boccia
Objective Various genome-wide association studies (GWASs) identified new head and neck cancer (HNC) susceptibility loci, although the evidence has not been systematically summarized. We performed a systematic review and meta-analyses of the GWASs to identify the most commonly reported genetic loci associated with a risk of HNC. Data Sources We searched the PubMed, ISI Web of Science, SCOPUS, and GWAS databases to retrieve eligible studies, in English or Italian, published until June 1, 2017. Review Methods Only GWASs reporting data on the association between single-nucleotide polymorphisms (SNPs) and HNC were included...
October 2018: Otolaryngology—Head and Neck Surgery
Talita Piassa Mafessoni, Carolina Eurich Mazur, José Miguel Amenábar
Currently one of the greater challenges is the diagnosis and treatment of cancer. Many studies address the genetic and metabolic aspects to support in early diagnosis and increase the survival of individuals at high risk. Individuals with Fanconi anemia can be included in this high risk group because they have a predisposition to develop head and neck cancer. The use of salivary enzymes as biomarkers to detect the changes in oral tissue at the initial phase seems viable, because saliva is easy to obtain, it moisture oral mucosa and cells metabolic compounds can be found on it...
October 2018: Medical Hypotheses
Yasmine Ghantous, Zaher Bahouth, Imad Abu El-Naaj
PURPOSE: Recurrent and metastatic Oral Squamous Cell Carcinoma (OSCC) is often incurable. There are large gaps in the understanding of the clinical course, biology and genetic biomarkers of OSCC which could help us identify patients with high-risk of recurrence who may benefit from intensified therapy or novel targeted therapy trials. The purpose of this study was to identify significant clinical, pathological and genomic risk factors for local recurrence in OSCC. PATIENTS AND METHODS: Molecular data sets and clinicopathological characteristics of 159 head and neck carcinoma patients were obtained from The Cancer Genome Atlas (TCGA) data portal and analyzed using the Genome Data Analysis Center and cBioPortal to find significant risk factors for tumor recurrence...
August 6, 2018: Archives of Oral Biology
Tomonori Sasahira, Tadaaki Kirita
Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth leading malignancy worldwide. OSCC is an aggressive tumor and its prognosis has exhibited little improvement in the last three decades. Comprehensive elucidation of OSCC's molecular mechanism is imperative for early detection and treatment, improving patient survival. Based on broadly accepted notions, OSCC arises from multiple genetic alterations caused by chronic exposure to carcinogens. In 2011, research revealed 10 key alterations fundamental to cancer cell development: sustaining proliferative signaling, evading growth suppressors, avoiding immune destruction, activating invasion and metastasis, tumor-promoting inflammation, enabling replicative immortality, inducing angiogenesis, genome instability and mutation, resisting cell death, and deregulating energetics...
August 16, 2018: International Journal of Molecular Sciences
Ying Wang, Changli Yue, Jugao Fang, Lili Gong, Meng Lian, Ru Wang, Ling Feng, Hongzhi Ma, Zhihong Ma, Honggang Liu
Background: Hypopharyngeal squamous cell carcinoma (HPSCC) is an aggressive head and neck squamous cell carcinoma with poor prognosis. Neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy could provide better efficacy in HPSCC treatment. Identification of predictive biomarkers is critically needed to improve selection of patients who derive the most benefit from NACT. The aim of this study was to investigate whether transcobalamin I (TCN1) could be a novel predictive biomarker for NACT in HPSCC...
2018: OncoTargets and Therapy
Hanibal Bohnenberger, Lars Kaderali, Philipp Ströbel, Diego Yepes, Uwe Plessmann, Neekesh V Dharia, Sha Yao, Carina Heydt, Sabine Merkelbach-Bruse, Alexander Emmert, Jonatan Hoffmann, Julius Bodemeyer, Kirsten Reuter-Jessen, Anna-Maria Lois, Leif Hendrik Dröge, Philipp Baumeister, Christoph Walz, Lorenz Biggemann, Roland Walter, Björn Häupl, Federico Comoglio, Kuan-Ting Pan, Sebastian Scheich, Christof Lenz, Stefan Küffer, Felix Bremmer, Julia Kitz, Maren Sitte, Tim Beißbarth, Marc Hinterthaner, Martin Sebastian, Joachim Lotz, Hans-Ulrich Schildhaus, Hendrik Wolff, Bernhard C Danner, Christian Brandts, Reinhard Büttner, Martin Canis, Kimberly Stegmaier, Hubert Serve, Henning Urlaub, Thomas Oellerich
Patients with head-and-neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head-and-neck (HNSCC) carcinomas by quantitative proteomics. In a training cohort, we quantified 4,957 proteins in 44 SQCLC and 30 HNSCC tumours. A total of 518 proteins were found to be differentially expressed between SQCLC and HNSCC, and some of these were identified as genetic dependencies in either of the two tumour types...
September 2018: EMBO Molecular Medicine
Patrick E Nyman, Darya Buehler, Paul F Lambert
Purpose: Head and neck squamous cell carcinoma (HNSCC), a common cancer worldwide, is etiologically associated with tobacco use, high alcohol consumption, and high-risk human papillomaviruses (HPV). The Notch signaling pathway, which is involved in cell differentiation decisions with differential downstream targets and effects depending on tissue type and developmental stage, has been implicated in human HNSCC. NOTCH1 is among the most frequently mutated genes in both HPV-positive and HPV-negative HNSCC. These mutations are predicted to inactivate the function of Notch...
August 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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