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Genetic Markers HNSCC

Cielito C Reyes-Gibby, Jian Wang, Mary Rose T Silvas, Robert K Yu, Ehab Y Hanna, Sanjay Shete
Pain is often one of the first signs of squamous cell carcinoma of the head and neck (HNSCC). Pain at diagnosis is an important prognostic marker for the development of chronic pain, and importantly, for the overall survival time. To identify variants influencing severe pre-treatment pain in 1,368 patients newly diagnosed with HNSCC, we conducted a genome-wide association study based on 730,525 tagging SNPs. The patients were all previously untreated for cancer. About 15% of the patients had severe pre-treatment pain, defined as pain score ≥7 (0 = "no pain" and 10 = "worst pain")...
September 27, 2016: Scientific Reports
Paolo Boscolo-Rizzo, Maria Cristina Da Mosto, Enrica Rampazzo, Silvia Giunco, Annarosa Del Mistro, Anna Menegaldo, Lorena Baboci, Monica Mantovani, Giancarlo Tirelli, Anita De Rossi
Strongly associated with tobacco use, heavy alcohol consumption, and with high-risk human papillomavirus (HPV) infection, head and neck squamous cell carcinoma (HNSCC) is a frequently lethal, heterogeneous disease whose pathogenesis is a multistep and multifactorial process involving genetic and epigenetic events. The majority of HNSCC patients present with locoregional advanced stage disease and are treated with combined modality strategies that can markedly impair quality of life and elicit unpredictable results...
September 2016: Cancer Metastasis Reviews
Lin-Lin Bu, Guang-Tao Yu, Wei-Wei Deng, Liang Mao, Jian-Feng Liu, Si-Rui Ma, Teng-Fei Fan, Bradford Hall, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
Cumulative evidence suggests that constitutively activated signal transducer and activator of transcription (STAT3) may contribute to sustaining immunosuppressive status, and that inhibiting STAT3 signaling represents a potential strategy to improve antitumor immunity. In the present study, we observed that high levels phosphorylated of STAT3 are significantly associated with the markers for both myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in human head and neck squamous cell carcinoma (HNSCC)...
May 2016: Oncoimmunology
Munindra Ruwali, Ankur Dhawan, Mohan C Pant, Qamar Rahman, S M Paul Khurana, Devendra Parmar
Head and neck squamous cell carcinoma (HNSCC) describes a wide range of malignant tumors which originate in the upper aerodigestive tract and have a multifactorial origin involving both genetic and lifestyle risk factors. The clinical management of head and neck cancer involves surgery, radiotherapy, and chemotherapy. With the advances in treatment strategies for HNSCC, newer targeted therapies are adding to the progress already achieved in the multimodality management of patients although the problems of differences in drug response and adverse drug reactions are still grave concerns...
2016: Oncology Research and Treatment
Johannes Doescher, Guido Piontek, Markus Wirth, Marcus Bettstetter, Juergen Schlegel, Bernhard Haller, Gero Brockhoff, Rudolf Reiter, Anja Pickhard
BACKGROUND: Sinonasal squamous-cell carcinomas (SNSCC) are relatively rare. Thus, data regarding the rate of lymph node metastases are inconsistent in contrast with well-known high metastasis rates in squamous-cell carcinomas of the head and neck (HNSCC) (oral cavity, pharynx and larynx). Hence, the indication for elective neck dissection is difficult in SNSCC. The aim of this study was to assess common genetic alterations and EBV and HPV status as a function of metastasis in SNSCC and HNSCC...
October 2015: Oral Oncology
Sang Hyuk Lee, Hyo Jung Nam, Hyun Jung Kang, Tina L Samuels, Nikki Johnston, Young Chang Lim
Emerging evidence suggests that cancer cells present profound epigenetic alterations in addition to featuring classic genetic mutations. Valproic acid (VPA), a histone deacetylase inhibitor, can potently inhibit tumor growth and induce differentiation. However, the effect and underlying mechanism of VPA on head and neck squamous cell carcinoma (HNSCC) cancer stem cells (CSCs) remain unclear. In the present study we investigated the effects of VPA on the characteristics of HNSCC CSCs in vitro and in vivo. As a result, VPA inhibited the self-renewal abilities of HNSCC CSCs during two serial passages and decreased the expression of stem cell markers, such as Oct4, Sox2 and CD44...
October 2015: Oncology Reports
Javed Hussain Choudhury, Sankar Kumar Ghosh
BACKGROUND: Epigenetic and genetic alteration plays a major role to the development of head and neck squamous cell carcinoma (HNSCC). Consumption of tobacco (smoking/chewing) and human papilloma virus (HPV) are also associated with an increase the risk of HNSCC. Promoter hypermethylation of the tumor suppression genes is related with transcriptional inactivation and loss of gene expression. We investigated epigenetic alteration (promoter methylation of tumor-related genes/loci) in tumor tissues in the context of genetic alteration, viral infection, and tobacco exposure and survival status...
2015: PloS One
James W Rocco
Intra-tumor heterogeneity, variation between individual tumor cells within a patient's tumor, is increasingly seen as a critical mechanism underlying treatment resistance and therapeutic failure. Despite this growing awareness, few methods to assess intra-tumor heterogeneity exist outside the research laboratory, especially in the absence of a known marker. Mutant allele tumor heterogeneity (MATH) is a novel, non-biased, quantitative method to assess genetic heterogeneity based on tumor next generation exome sequencing...
March 2015: Head and Neck Pathology
Masamichi Hayashi, Gaosong Wu, Jong-Lyel Roh, Xiaofei Chang, Xiufeng Li, Julie Ahn, Marla Goldsmith, Zubair Khan, Justin Bishop, Zhe Zhang, Xian Chong Zhou, Jeremy Richmon, Nishant Agrawal, Wayne M Koch
BACKGROUND: Securing negative surgical margins is a critical goal for head and neck surgery. Local recurrence develops even in some patients who have histologically negative surgical margins. Minimal residual tumor cells may lead to locoregional recurrence despite clear histologic margins reported at the time of resection of head and neck squamous cell carcinoma (HNSCC). To identify subclinical residual disease, the authors analyzed deep margin imprint samples collected on 1-layer nitrocellulose sheets...
June 15, 2015: Cancer
Belinda Hauser, Yuan Zhao, Xiaowu Pang, Zhiqiang Ling, Ernest Myers, Paul Wang, Joseph Califano, Xinbin Gu
BACKGROUND: Incidence of head and neck squamous cell carcinoma (HNSCC) has continuously increased in past years while its survival rate has not been significantly improved. There is a critical need to better understand the genetic regulation of HNSCC tumorigenesis and progression. In this study, we comprehensively analyzed the function of miRNA-128 (miR-128) in the regulation of HNSCC growth and its putative targets in vitro and in vivo systems. METHODS: The function and targets of miR-128 were investigated in human HNSCC cell lines (JHU-13 and JHU-22), which were stably transfected with the miR-128 gene using a lentiviral delivery system...
2015: PloS One
Guru Prasad Maiti, Amlan Ghosh, Pinaki Mondal, Aradhita Baral, Sayantan Datta, Sudip Samadder, Sandeep P Nayak, Jayanta Chakrabarti, Jaydeep Biswas, Nilabja Sikdar, Shantanu Chowdhury, Bidyut Roy, Susanta Roychowdhury, Chinmay Kumar Panda
Single nucleotide polymorphisms (SNPs) in the 3'-UTR region are emerging cis-regulatory factors associated with the occurrences of several human diseases. SH3GL2, which is located at chromosome 9p21-22, is associated with hyperplastic/mildly dysplastic lesions of the head and neck and has a long 3'-UTR with multiple SNPs. The aim of the present study was to determine the susceptible allele(s) in the 3'-UTR SNPs of SH3GL2 in head and neck squamous cell carcinoma (HNSCC). First, we screened the genotypes of all SNPs located in the 3'-UTR of SH3GL2 in 110 controls and 147 cases in Indian populations by sequencing...
May 2015: Biochimica et Biophysica Acta
Edmund A Mroz, Aaron D Tward, Aaron M Tward, Rebecca J Hammon, Yin Ren, James W Rocco
BACKGROUND: Although the involvement of intra-tumor genetic heterogeneity in tumor progression, treatment resistance, and metastasis is established, genetic heterogeneity is seldom examined in clinical trials or practice. Many studies of heterogeneity have had prespecified markers for tumor subpopulations, limiting their generalizability, or have involved massive efforts such as separate analysis of hundreds of individual cells, limiting their clinical use. We recently developed a general measure of intra-tumor genetic heterogeneity based on whole-exome sequencing (WES) of bulk tumor DNA, called mutant-allele tumor heterogeneity (MATH)...
February 2015: PLoS Medicine
Lusia Sepiashvili, Jeff P Bruce, Shao Hui Huang, Brian O'Sullivan, Fei-Fei Liu, Thomas Kislinger
Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous disease that develops via one of the two primary carcinogenic routes: chemical carcinogenesis through exposure to tobacco and alcohol or virally induced tumorigenesis. Human papillomavirus (HPV)-positive (HPV(+)) and HPV-negative (HPV(-)) HNSCCs represent distinct clinical entities, with the latter associated with significantly inferior outcome. The biologic basis of these different outcomes is an area of intense investigation; their therapeutic regimens are currently also being reevaluated, which would be significantly facilitated by reliable biomarkers for stratification...
February 1, 2015: Cancer Research
Xiao-Yun Zhang, Minle Li, Kai Sun, Xiao-Jie Chen, Jian Meng, Lifang Wu, Ping Zhang, Xuemei Tong, Wei-Wen Jiang
To identify novel tumor suppressor genes that are down-regulated by promoter hypermethylation in head and neck squamous cell carcinoma (HNSCC), genome-wide methylation profiling was performed using a methylated DNA immunoprecipitation (MeDIP) array in HNSCC and normal mucosa tissue samples. Promoter hypermethylation of the candidate gene, gene associated with retinoid-interferon induced mortality-19 (GRIM-19), was confirmed in HNSCC cell lines. Multivariate regression analysis determined that GRIM-19 hypermethylation was an independent significant factor for HNSCC diagnosis (OR:125...
January 1, 2015: Oncotarget
Andrew Feber, Manit Arya, Patricia de Winter, Muhammad Saqib, Raj Nigam, Peter R Malone, Wei Shen Tan, Simon Rodney, Matthias Lechner, Alex Freeman, Charles Jameson, Asif Muneer, Stephan Beck, John D Kelly
PURPOSE: Penile cancer is a rare malignancy in the developed world with just more than 1,600 new cases diagnosed in the United States per year; however, the incidence is much higher in developing countries. Although HPV is known to contribute to tumorigenesis, little is known about the genetic or epigenetic alterations defining penile cancer. EXPERIMENTAL DESIGN: Using high-density genome-wide methylation arrays, we have identified epigenetic alterations associated with penile cancer...
March 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Florian Clatot, Marie Cornic, Anca Berghian, Vinciane Marchand, Olivier Choussy, Faissal El Ouakif, Arnaud François, Philippe Ruminy, Sophie Laberge-Le-Couteulx, Jean-Michel Picquenot, Fabrice Jardin
The CXCL12/CXCR4 axis is involved in numerous models of metastatic dissemination, including head and neck squamous cell carcinoma (HNSCC). We assessed the relative expressions of CXCL12, CXCR4 and CXCR7 in the stroma and the tumour of HNSCC, and evaluated the methylation status of the CXCL12 promoter.Snap-frozen, HPV negative HNSCC samples were micro-dissected to isolate the tumoural and stromal compartments. The expression levels of CXCL12, CXCR4 and CXCR7 were assessed by qRT-PCR, and the methylation level of the CXCL12 promoter was evaluated by pyrosequencing...
January 2015: Pathology
Hyunseok Kang, Ana Kiess, Christine H Chung
Head and neck cancer (HNC) broadly includes carcinomas arising from the mucosal epithelia of the head and neck region as well as various cell types of salivary glands and the thyroid. As reflected by the multiple sites and histologies of HNC, the molecular characteristics and clinical outcomes of this disease vary widely. In this Review, we focus on established and emerging biomarkers that are most relevant to nasopharyngeal carcinoma and head and neck squamous-cell carcinoma (HNSCC), which includes primary sites in the oral cavity, oropharynx, hypopharynx and larynx...
January 2015: Nature Reviews. Clinical Oncology
A Coordes, S Zhifeng, V Sangvatanakul, X Qian, M Lenarz, A M Kaufmann, A E Albers
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. HNSCC is caused by persistent high-risk human papillomavirus (HR-HPV) infection or excessive consumption of alcohol or tobacco. The persistently low survival rates result from local recurrences and metastases, which are probably caused by so-called tumor stem cells (TSCs). The epithelial-mesenchymal transition (EMT) or transformation is a key event in metastasis initiation and is being increasingly associated with TSCs...
December 2014: HNO
Ken-ichi Aoyama, Yoshihide Ota, Kagemasa Kajiwara, Noriaki Hirayama, Minoru Kimura
Recent studies showed that head and neck squamous cell carcinoma (HNSCC) including oral squamous cell carcinoma (OSCC) of Caucasian, Chinese and Indian patients frequently have NOTCH1 mutations. We found eight of 84 OSCC in Japanese patients have point mutations (9.5%) correspond to the ligand binding region of NOTCH1 protein. Two set of them are the same mutations and all mutations are non-synonymous G>A transitions. In addition, median disease-free survival is significantly longer in patients with NOTCH1-mutated tumors as compared to those without the mutation (P<0...
October 3, 2014: Biochemical and Biophysical Research Communications
Susanne M Gollin
Cytogenetic alterations underlie the development of head and neck squamous cell carcinoma (HNSCC), whether tobacco and alcohol use, betel nut chewing, snuff or human papillomavirus (HPV) causes the disease. Many of the molecular genetic aberrations in HNSCC result from these cytogenetic alterations. This review presents a brief introduction to the epidemiology of HNSCC, and discusses the role of HPV in the disease, cytogenetic alterations and their frequencies in HNSCC, their molecular genetic and The Cancer Genome Atlas (TCGA) correlates, prognostic implications, and possible therapeutic considerations...
December 2014: Genes, Chromosomes & Cancer
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