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Head and neck cancer genetics

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...
August 10, 2018: EMBO Molecular Medicine
Patrick 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...
August 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yong-Jiang Li, Yong Luo, Xiao-Qi Xie, Ping Li, Feng Wang
BACKGROUND AND PURPOSE: The prognostic significance of circulating tumor cells (CTCs) in head and neck cancer is still under debate, as only a few studies have been reported and limited conclusions are reached. Besides, CTCs' count alone was utilized as an indicator in the previous researches. As a form of 'liquid biopsy', the further identification of genetic or phenotypic biomarkers on CTCs could possibly provide further clinical significance. MATERIALS AND METHODS: The prospective study enrolled 131 patients with nasopharyngeal carcinoma (NPC)...
August 3, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
L Salazar-García, M Pérez-Sayáns, A García-García, A Carracedo, R Cruz, A Lozano, B Sobrino, F Barros
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a global public health problem, which increases in prevalence every year. Evidence brings up that small populations of stem cells, the cancer stem cells (CSC), are responsible for tumour initiation, tumorigenesis, progression, and metastasis. These cells play a crucial role in cancer development and treatment response, but the origin of CSCs remains unclear. In this research, we have sequenced the entire exome of the three different groups of cells of primary squamous cell carcinoma tumour from different patients, with the aim to understand their main genetic changes and to elucidate the possible origin of tumour cells and tumour stem cells...
August 1, 2018: Journal of Oral Pathology & Medicine
Tingting Qin, Yanxiao Zhang, Katie R Zarins, Tamara R Jones, Shama Virani, Lisa A Peterson, Jonathan B McHugh, Douglas Chepeha, Gregory T Wolf, Laura S Rozek, Maureen A Sartor
While whole-exome DNA sequencing is the most common technology to study genetic variants in tumors in known exonic regions, RNA-seq is cheaper, covers most of the same exonic regions, and is often more readily available. In this study, we show the utility of mRNA-seq-based variant analysis combined with targeted gene sequencing performed on both tumor and matched blood as an alternative when exome data is unavailable. We use the approach to study expressed variant profiles in the well-characterized University of Michigan (UM) head and neck squamous carcinoma (HNSCC) cohort (n = 36)...
July 30, 2018: Scientific Reports
Linda Kachuri, Olli Saarela, Stig Egil Bojesen, George Davey Smith, Geoffrey Liu, Maria Teresa Landi, Neil E Caporaso, David C Christiani, Mattias Johansson, Salvatore Panico, Kim Overvad, Antonia Trichopoulou, Paolo Vineis, Ghislaine Scelo, David Zaridze, Xifeng Wu, Demetrius Albanes, Brenda Diergaarde, Pagona Lagiou, Gary J Macfarlane, Melinda C Aldrich, Adonina Tardón, Gad Rennert, Andrew F Olshan, Mark C Weissler, Chu Chen, Gary E Goodman, Jennifer A Doherty, Andrew R Ness, Heike Bickeböller, H-Erich Wichmann, Angela Risch, John K Field, M Dawn Teare, Lambertus A Kiemeney, Erik H F M van der Heijden, June C Carroll, Aage Haugen, Shanbeh Zienolddiny, Vidar Skaug, Victor Wünsch-Filho, Eloiza H Tajara, Raquel Ayoub Moysés, Fabio Daumas Nunes, Stephen Lam, Jose Eluf-Neto, Martin Lacko, Wilbert H M Peters, Loïc Le Marchand, Eric J Duell, Angeline S Andrew, Silvia Franceschi, Matthew B Schabath, Jonas Manjer, Susanne Arnold, Philip Lazarus, Anush Mukeriya, Beata Swiatkowska, Vladimir Janout, Ivana Holcatova, Jelena Stojsic, Dana Mates, Jolanta Lissowska, Stefania Boccia, Corina Lesseur, Xuchen Zong, James D McKay, Paul Brennan, Christopher I Amos, Rayjean J Hung
Background: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. Methods: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects...
July 28, 2018: International Journal of Epidemiology
Alexandra Iulia Irimie, Cornelia Braicu, Roxana Cojocneanu, Lorand Magdo, Anca Onaciu, Cristina Ciocan, Nikolay Mehterov, Diana Dudea, Smaranda Buduru, Ioana Berindan-Neagoe
Smoking is a well-known behavior that has an important negative impact on human health, and is considered to be a significant factor related to the development and progression of head and neck squamous cell carcinomas (HNSCCs). Use of high-dimensional datasets to discern novel HNSCC driver genes related to smoking represents an important challenge. The Cancer Genome Atlas (TCGA) analysis was performed in three co-existing groups of HNSCC in order to assess whether gene expression landscape is affected by tobacco smoking, having quit, or non-smoking status...
July 23, 2018: International Journal of Environmental Research and Public Health
Sanjay Singh, Manish Gupta, Ambika Sharma, Rajeev Kumar Seam, Harish Changotra
AIM: The early gene factor-2 (E2F), a family of transcription factors, is involved in cell cycle regulation. Deregulated expression of most of the members of the E2F family is associated with various human cancers. In this study, we investigated the association between the E2F1 genetic variants rs3213173 (C/T) (Val276Met) and rs3213176 (G/A) (Gly393Ser) with the risk of lung cancer (LC) and head and neck cancer (HNC) in 190 patients and 230 control samples. MATERIALS AND METHODS: We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and mutagenic primer-based PCR-RFLP methods to genotype all target polymorphisms...
July 23, 2018: Genetic Testing and Molecular Biomarkers
Brandon L Pierce, Peter Kraft, Chenan Zhang
Purpose of review: In this paper, we summarize prior studies that have used Mendelian Randomization (MR) methods to study the effects of exposures, lifestyle factors, physical traits, and/or biomarkers on cancer risk in humans. Many such risk factors have been associated with cancer risk in observational studies, and the MR approach can be used to provide evidence as to whether these associations represent causal relationships. MR methods require a risk factor of interest to have known genetic determinants that can be used as proxies for the risk factor (i...
June 2018: Current Epidemiology Reports
HuanHuan Guo, Shuo Huang, Shuang Li, Hui Yu, ShiXiong Wu, XuHong Zhou
Background and objective: Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy. Despite recent advances in treatment, the prognosis, particularly for those at the advanced stages, remains poor. Moreover, the underlying genetic and molecular events have remained obscure so far. Recently, increasing evidence has demonstrated that long noncoding RNAs (lncRNAs) could act as either oncogenes or tumor suppressor genes in various cancers depending on their targets. And some lncRNAs have been shown to be aberrantly expressed in NPC...
2018: Cancer Management and Research
Daniel Martin, Maria S Degese, Lynn Vitale-Cross, Ramiro Iglesias-Bartolome, Juan Luis Callejas Valera, Zhiyong Wang, Xiaodong Feng, Huwate Yeerna, Vachan Vadmal, Toshiro Moroishi, Rick F Thorne, Moraima Zaida, Bradford Siegele, Sok C Cheong, Alfredo A Molinolo, Yardena Samuels, Pablo Tamayo, Kun Liang Guan, Scott M Lippman, J Guy Lyons, J Silvio Gutkind
Dysregulation of the Hippo signaling pathway and the consequent YAP1 activation is a frequent event in human malignancies, yet the underlying molecular mechanisms are still poorly understood. A pancancer analysis of core Hippo kinases and their candidate regulating molecules revealed few alterations in the canonical Hippo pathway, but very frequent genetic alterations in the FAT family of atypical cadherins. By focusing on head and neck squamous cell carcinoma (HNSCC), which displays frequent FAT1 alterations (29...
July 9, 2018: Nature Communications
A Paderno, R Morello, C Piazza
A recent reduction in the number of smoke-related tumours has been observed thanks to the diffusion of anti-tobacco campaigns carried out in the majority of developed countries. Nevertheless, as demonstrated by recent global epidemiologic studies, squamous cell carcinoma of the mobile tongue appears to be progressively increasing in incidence, particularly among young adults and especially in females. The driving mechanism responsible for such changes is still to be precisely defined. Several genetic studies have compared the mutational pattern of tongue squamous cell carcinoma in young adults to that of more elderly patients, without identifying significant differences that may help in better characterising this subgroup of subjects...
June 2018: Acta Otorhinolaryngologica Italica
Tatiana Lepikhova, Piia-Riitta Karhemo, Riku Louhimo, Bhagwan Yadav, Astrid Murumägi, Evgeny Kulesskiy, Mikko Kivento, Harri Sihto, Reidar Grénman, Stina M Syrjänen, Olli Kallioniemi, Tero Aittokallio, Krister Wennerberg, Heikki Joensuu, Outi Monni
There is an unmet need for effective targeted therapies for patients with advanced head and neck squamous cell carcinoma (HNSCC). We correlated gene expression, gene copy numbers and point mutations in 45 human papillomavirus negative HNSCC cell lines with the sensitivity to 220 anticancer drugs to discover predictive associations to genetic alterations. The drug response profiles revealed diverse efficacy of the tested drugs across the cell lines. Several genomic abnormalities and gene expression differences were associated with response to mTOR, MEK and EGFR inhibitors...
July 3, 2018: Molecular Cancer Therapeutics
Philipp Opitz, Olf Herbarth
BACKGROUND: Different organisms such as bacteria, molds and humans produce and release a relative unknown class of metabolites which are responsible for the individual olfactory pattern. These volatile organic metabolites (VOM) represent a kind of biosignature that reflects the sum of all multifactorial influences, including genetics, environmental factors, nutritional and disease status. As a result of pathological processes the individual body odor can be influenced by newly produced or altered compositions of the VOM...
July 3, 2018: Journal of Otolaryngology—Head & Neck Surgery
Chun-Wen Su, Ming-Hsien Chien, Chiao-Wen Lin, Mu-Kuan Chen, Jyh-Ming Chow, Chun-Yi Chuang, Chia-Hsuan Chou, Yu-Cheng Liu, Shun-Fa Yang
Oral cancer is a major head and neck cancer that is reported to be causally associated with genetic factors and environmental carcinogens. Endothelial nitric oxide synthase (eNOS) was reported to modulate carcinogenesis and progression through nitric oxide (NO) production. Genetic polymorphisms in the eNOS gene can regulate its transcription and further mediate NO production. The purpose of this study was to explore the influences of eNOS gene polymorphisms combined with environmental carcinogens on the predisposition for oral cancer...
June 20, 2018: Nitric Oxide: Biology and Chemistry
Jialing Zhang, Tony Chen, Xinping Yang, Hui Cheng, Stephan S Späth, Paul E Clavijo, Jianhong Chen, Christopher Silvin, Natalia Issaeva, Xiulan Su, Wendell G Yarbrough, Christina M Annunziata, Zhong Chen, Carter Van Waes
Human papilloma viruses (HPV) are linked to an epidemic increase in oropharyngeal head and neck squamous cell carcinomas (HNSCC), which display viral inactivation of tumor suppressors TP53 and RB1 and rapid regional spread. However, the role of genomic alterations in enabling modulation of pathways that promote the aggressive phenotype of these cancers is unclear. Recently, a subset of HPV+ HNSCC has been shown to harbor novel genetic defects or decreased expression of TNF-receptor-associated-factor-3 (TRAF3)...
June 19, 2018: Cancer Research
Sarah Emmett, David C Whiteman, Benedict J Panizza, Annika Antonsson
Squamous cell carcinoma of mucosal sites in the head and neck (HNSCC) is the sixth most common cause of cancer worldwide, and despite advances in conventional management, it still has significant morbidity and mortality associated with both diagnosis and treatment. Advances in our understanding of the biological mechanisms underlying this disease have demonstrated a significant difference between human papillomavirus (HPV)-associated, HPV and tobacco associated, and HPV-negative disease. It remains important to further elucidate the biologic and genetic differences between HPV-associated and tobacco-associated disease, with the aim of earlier diagnosis through screening, and advances in management including the development of novel therapeutic agents...
June 19, 2018: Oncology
Claus Wittekindt, Steffen Wagner, Shachi Jenny Sharma, Nora Würdemann, Jennifer Knuth, Henrike Reder, Jens Peter Klußmann
Head and neck cancer is the sixth most common cancer with over 500000 annually reported incident cases worldwide. Besides major risk factors tobacco and alcohol, oropharyngeal squamous cell carcinomas (OSCC) show increased association with human papillomavirus (HPV). HPV-associated and HPV-negative OSCC are 2 different entities regarding biological characteristics, therapeutic response, and patient prognosis. In HPV OSCC, viral oncoprotein activity, as well as genetic (mutations and chromosomal aberrations) and epigenetic alterations plays a key role during carcinogenesis...
March 2018: Laryngo- Rhino- Otologie
Sambit Swarup Nanda, Ajeet Kumar Gandhi, Madhup Rastogi, Rohini Khurana, Rahat Hadi, Kamal Sahni, Surendra Prasad Mishra, Anoop K Srivastava, Madan Lal Brahma Bhatt, Devendra Parmar
PURPOSE: We evaluated the correlation of the x-ray repair cross complementing gene 1 (XRCC1) Arg194Trp polymorphism with clinical outcomes in head and neck squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiation therapy (CCRT). METHODS AND MATERIALS: In this prospective cohort study, we included 101 patients with HNSCC (oral cavity, pharynx, and larynx) who were aged ≥ 18 years, had stage III to IVB disease, had a Karnofsky Performance Status ≥ 80, and were deemed fit for CCRT...
July 1, 2018: International Journal of Radiation Oncology, Biology, Physics
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