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| Open AccessDevelopment of high-throughput ATR-FTIR technology for rapid triage of brain cancer
Diagnosing brain cancer is frequently difficult and requires specialist equipment. Here, the authors develop their previous attenuated total reflectance-Fourier transform infrared spectroscopy method and incoporate the use of disposable silicon wafers for diagnosing brain cancer using serum samples.
- Holly J. Butler
- , Paul M. Brennan
- & Matthew J. Baker
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| Open AccessLiquid biopsy tracking during sequential chemo-radiotherapy identifies distinct prognostic phenotypes in nasopharyngeal carcinoma
Liquid biopsies are emerging as a useful method for diagnosis and prognosis in cancer. Here, the authors show the prognostic value of monitoring the level of circulating Epstein-barr virus DNA throughout induction chemotherapy and chemo-radiotherapy and its potential utility for risk-adapted individualised therapy in nasopharyngeal carcinomapatients.
- Jiawei Lv
- , Yupei Chen
- & Ying Sun
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| Open AccessMethylation analysis of plasma DNA informs etiologies of Epstein-Barr virus-associated diseases
Epstein-Barr virus (EBV) is associated with different malignant diseases and circulating EBV DNA is a biomarker for nasopharyngeal carcinoma (NPC). Here, the authors report that plasma EBV DNA methylation profiles show disease-associated patterns and can help to distinguish NPC and non-NPC subjects.
- W. K. Jacky Lam
- , Peiyong Jiang
- & Y. M. Dennis Lo
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| Open AccessChromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers
In tumours aberrant epigenetic modifications can alter the transcriptional state. Here, the authors identify a common tumour-specific shift to transcriptional repression associated with DNA methylation and chromatin dysregulation at the transcription start site.
- Mizuo Ando
- , Yuki Saito
- & Joseph A. Califano
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| Open AccessEnhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands
Acinic cell carcinoma (AciCC) is a rare salivary gland carcinoma that is poorly understood. Here the authors perform genomic, transcriptomic and epigenomic profiling of AciCC and find highly recurrent and specific rearrangements [t(4;9)(q13;q31)], which lead to enhancer hijacking that activates oncogenic transcription factor NR4A3.
- Florian Haller
- , Matthias Bieg
- & Abbas Agaimy
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| Open AccessGenomic analysis identifies frequent deletions of Dystrophin in olfactory neuroblastoma
Olfactory neuroblastoma (ONB) is a rare malignant tumor whose genetic basis is poorly understood. Here the authors identify recurrent deletions involving dystrophin in the majority of ONB patient tumors examined.
- Gary L. Gallia
- , Ming Zhang
- & Chetan Bettegowda
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| Open AccessEstablishment and characterization of new tumor xenografts and cancer cell lines from EBV-positive nasopharyngeal carcinoma
The lack of appropriate models restricts pre-clinical research for nasopharyngeal carcinoma (NPC). Here the authors report the development and characterization of NPC patient-derived xenografts (PDXs), and EBV positive NPC cell line from patient tumor, and suggest their potential use in future NPC research.
- Weitao Lin
- , Yim Ling Yip
- & Sai Wah Tsao
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| Open AccessCancer exosomes induce tumor innervation
Tumors can induce axonogenesis which is commonly associated with worse outcomes. Here, the authors show that this phenomenon is mediated by cancer exosomes.
- Marianna Madeo
- , Paul L. Colbert
- & Paola D. Vermeer
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| Open AccessCo-activation of super-enhancer-driven CCAT1 by TP63 and SOX2 promotes squamous cancer progression
Master regulator transcription factors TP63 and SOX2 have been reported to overlap in genomic occupancy in squamous cell carcinomas (SCCs). Here, the authors demonstrate that TP63 and SOX2 promote co-operatively long non-coding RNA CCAT1 expression through activating its super-enhancer, and CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR super-enhancers and enhances both the MEK/ERK1/2 and PI3K/AKT signaling pathways in SCC.
- Yuan Jiang
- , Yan-Yi Jiang
- & H. Phillip Koeffler
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| Open AccessCombining discovery and targeted proteomics reveals a prognostic signature in oral cancer
Oral cancer has region-specific histopathological and molecular characteristics, complicating its classification by the standard tumor-node-metastasis system. Here, the authors combine discovery and targeted proteomics with IHC to identify region-specific and saliva biomarkers for oral cancer prognosis.
- Carolina Moretto Carnielli
- , Carolina Carneiro Soares Macedo
- & Adriana Franco Paes Leme
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| Open AccessImmunomodulatory role of Keratin 76 in oral and gastric cancer
Keratin 76 (Krt76) is an epithelial differentiation marker that is downregulated in oral squamous cell carcinomas, correlating with poor prognosis. Here the authors show that genetic ablation of Krt76 in a mouse model results in increased susceptibility to carcinogenesis via enhanced accumulation of Tregs.
- Inês Sequeira
- , Joana F. Neves
- & Fiona M. Watt
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| Open AccessNSD1- and NSD2-damaging mutations define a subset of laryngeal tumors with favorable prognosis
The authors use an integrative clustering approach to identify two laryngeal cancer clusters with distinct prognosis and show that mutations damaging the NSD1 and NSD2 methyltransferases segregate to the cluster with favorable prognosis, and independently predict longer survival in patients with laryngeal, but not other head and neck cancers.
- Suraj Peri
- , Evgeny Izumchenko
- & Erica A. Golemis
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| Open AccessFbxo4-mediated degradation of Fxr1 suppresses tumorigenesis in head and neck squamous cell carcinoma
Fbxo4 tumour suppressor is part of a SCF E3 ligase which has two known substrates. Here, the authors identify Fxr1 as a substrate of SCFFbxo4 and identify an inherent regulatory feedback loop in head and neck squamous cell carcinoma that results in the bypass of senescence and neoplastic progression.
- Shuo Qie
- , Mrinmoyee Majumder
- & J. Alan Diehl
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| Open AccessMulti-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions
Myoepithelial carcinoma (MECA) is a rare aggressive salivary gland cancer. Here, the authors analyze the genomic landscape of MECA and identify a high prevalence of oncogenic gene fusions, primarily PLAG1 fusions, highlighting TGFBR3-PLAG1 as a potential hallmark of MECA.
- Martin G. Dalin
- , Nora Katabi
- & Luc G. T. Morris
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| Open AccessTumour-specific PI3K inhibition via nanoparticle-targeted delivery in head and neck squamous cell carcinoma
Head and neck squamous cell carcinomas (HNSCC) often harbourPIK3CAmutations but PI3Kα inhibitors can cause some side effects. Here, the authors develop P-selectin targeted nanoparticles to enhance tumour-specific delivery of a PI3Kα inhibitor to HNSCC PDX and orthotopic xenograft models.
- Aviram Mizrachi
- , Yosi Shamay
- & Maurizio Scaltriti
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| Open AccessHOPX hypermethylation promotes metastasis via activating SNAIL transcription in nasopharyngeal carcinoma
HOPX is a transcription factor epigenetically silenced in several cancers. Here the authors, by analysing methylation profiles, identify HOPX as a suppressor of metastasis in nasopharyngeal carcinoma: mechanistically HOPX inhibitsSNAILtranscription through deacetylation-mediated silencing.
- Xianyue Ren
- , Xiaojing Yang
- & Jun Ma
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| Open AccessFibronectin-guided migration of carcinoma collectives
Tumour microenvironment influences the migration of cancer cells. Here the authors analyse the proteomic constitution of the extracellular matrix and identify a role for fibronectin in regulating the collective migration of squamous cell carcinoma cells.
- Sandeep Gopal
- , Laurence Veracini
- & Ellen Van Obberghen-Schilling
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| Open AccessExome and genome sequencing of nasopharynx cancer identifies NF-κB pathway activating mutations
Nasopharyngeal cancer is frequently characterized by Epstein-Barr virus infection. Here, using genomic analyses, the authors find that the tumours harbour mutations in genes involved in the NF-κB signalling pathway or overexpress a viral oncoprotein, latent membrane protein 1.
- Yvonne Y Li
- , Grace T. Y. Chung
- & Kwok-Wai Lo
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| Open AccessmiR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR–p-PI3K/AKT-c-JUN
Although miR-related mechanisms have been implicated in nasopharyngeal carcinoma (NPC), a precise role for miR-3188 has not been reported in this context. Here, Zhao et al. show that FOXO1-induced miR-3188 acts as a tumour suppressor in NPC by regulating the axis mTOR/PI3K/Akt/c-Jun.
- Mengyang Zhao
- , Rongcheng Luo
- & Weiyi Fang
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| Open AccessStabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers
The molecular pathways involving p21 and mTORC1 are frequently deregulated in head and neck squamous cell carcinomas (HNSCC). Here, Llanos et al. report a mechanism that regulates p21 stability through the mTORC1/4E-BP1 pathway independently of p53, and show that the mechanism is prevalent in HNSCC.
- Susana Llanos
- , Juana M. García-Pedrero
- & Manuel Serrano
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| Open AccessEpstein–Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma
Epstein–Barr virus is associated with nasopharyngeal carcinoma and previous studies have focused on the role of viral proteins in tumour pathology. Here, the authors show that a viral miRNA targets the host protein PTEN and has a critical role in the late stage of nasopharyngeal carcinoma by driving tumour metastasis.
- Longmei Cai
- , Yanfen Ye
- & Xin Li
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Galanin modulates the neural niche to favour perineural invasion in head and neck cancer
Perineural invasion occurs in many head and neck cancers and is thought to be an active process where tumour cells degrade the neural sheath. Here the authors show that the neuropeptide galanin mediates the crosstalk between nerves and cancer cells to promote malignant progression.
- Christina Springstead Scanlon
- , Rajat Banerjee
- & Nisha J. D’Silva
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| Open AccessNeuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells
Epstein–Barr virus (EBV) is involved in the development of some cancers including nasopharyngeal carcinoma. Here, the authors show that a direct interaction between the viral protein gB and a host protein, neuropilin 1, is required for EBV infection of nasopharyngeal epithelial cells.
- Hong-Bo Wang
- , Hua Zhang
- & Mu-Sheng Zeng
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Somatic mutations in arachidonic acid metabolism pathway genes enhance oral cancer post-treatment disease-free survival
Chemical inhibitors of the tumour-progression promoting arachidonic acid metabolism pathway prolong post-treatment survival of cancer patients. Here the authors analyse sequence variation in oral cancer patients and show that loss-of-function mutations in this pathway prolong survival.
- Nidhan K. Biswas
- , Subrata Das
- & Partha P. Majumder
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TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer
Squamous cell carcinoma of the head and neck often becomes resistant to treatment. In this study, Banerjee et al. show that the ATPase TRIP13 can mediate resistance in cells from these tumours by inducing error prone non-homologous end joining DNA repair.
- Rajat Banerjee
- , Nickole Russo
- & Nisha J. D’Silva
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IKKα restoration via EZH2 suppression induces nasopharyngeal carcinoma differentiation
Nasopharyngeal carcinomas often present as undifferentiated tumours. Here, Yan et al. show that reduced expression of IKK via promoter methylation results in the undifferentiated phenotype of the tumours and that treatment with retinoic acid can reverse these features.
- Min Yan
- , Yan Zhang
- & Quentin Liu
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| Open AccessMutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups
Gingivo-buccal oral squamous cell carcinoma (OSCC-GB) is the leading cancer among males in India. Here, the authors carry out exome sequencing and recurrence testing in patients with OSCC-GB and highlight genes and biological pathways associated with the disease.
- Arindam Maitra
- , Nidhan K. Biswas
- & D. Sutradhar
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Cell–cell adhesion genes CTNNA2 and CTNNA3 are tumour suppressors frequently mutated in laryngeal carcinomas
Laryngeal carcinoma is a heterogeneous disease and multiple genes have been implicated in its pathogenesis. Here, Fanjul-Fernández et al. identify mutations in the cell–cell adhesion genes catenin α2 and catenin α3 in 15% of a cohort of homogeneous laryngeal carcinomas.
- Miriam Fanjul-Fernández
- , Víctor Quesada
- & Carlos López-Otín