Epigenetic Dysregulation in Laryngeal Squamous Cell Carcinoma

Wong, Thian‐Sze; Gao, Wei; Li, Zenghong; Chan, Jimmy Yu‐Wai; Ho, Wai Yin

doi:10.1155/2012/739461

Cited by 20 publications

(22 citation statements)

References 124 publications

(122 reference statements)

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“…Many of these genes were already known to be involved in important functions, including apoptosis, the cell cycle, cell migration, and invasion (for reviews see refs. 28,29). Interestingly, a recent analysis has shown that a protein involved in cell adhesion (cadherin 11) is specifically methylated in metastases (30).…”

Section: Discussionmentioning

confidence: 99%

A Poor Prognosis Subtype of HNSCC Is Consistently Observed across Methylome, Transcriptome, and miRNome Analysis

Jung

Job

Ledrappier

et al. 2013

Clinical Cancer Research

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Purpose: Distant metastasis after treatment is observed in about 20% of squamous cell carcinoma of the head and neck (HNSCC). In the absence of any validated robust biomarker, patients at higher risk for metastasis cannot be provided with tailored therapy. To identify prognostic HNSCC molecular subgroups and potential biomarkers, we have conducted genome-wide integrated analysis of four omic sets of data.Experimental Design: Using state-of-the-art technologies, a core set of 45 metastasizing and 55 nonmetastasizing human papillomavirus (HPV)-unrelated HNSCC patient samples were analyzed at four different levels: gene expression (transcriptome), DNA methylation (methylome), DNA copy number (genome), and microRNA (miRNA) expression (miRNome). Molecular subgroups were identified by a model-based clustering analysis. Their clinical relevance was evaluated by survival analysis, and functional significance by pathway enrichment analysis.Results: Patient subgroups selected by transcriptome, methylome, or miRNome integrated analysis are associated with shorter metastasis-free survival (MFS). A common subgroup, R1, selected by all three omic approaches, is statistically more significantly associated with MFS than any of the single omic-selected subgroups. R1 and non-R1 samples display similar DNA copy number landscapes, but more frequent chromosomal aberrations are observed in the R1 cluster (especially loss at 13q14.2-3). R1 tumors are characterized by alterations of pathways involved in cell-cell adhesion, extracellular matrix (ECM), epithelial-to-mesenchymal transition (EMT), immune response, and apoptosis.Conclusions: Integration of data across several omic profiles leads to better selection of patients at higher risk, identification of relevant molecular pathways of metastasis, and potential to discover biomarkers and drug targets. Clin Cancer Res; 19(15); 4174-84. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 99%

A Poor Prognosis Subtype of HNSCC Is Consistently Observed across Methylome, Transcriptome, and miRNome Analysis

Jung

Job

Ledrappier

et al. 2013

Clinical Cancer Research

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“…1 The definite cause of laryngeal cancer is not yet determined, although some risk factors, such as tobacco and alcohol consumption, genetic and epigenetic alterations are believed to be linked with the development of this disease. 2,3 Telomerase reverse transcriptase (TERT) gene, which encodes the catalytic subunit of telomerase, has been demonstrated to be up-regulated in human cancers, contributing to carcinogenesis. 4 Recently, two recurrent somatic mutations (1,295,228 C>T and 1,295,250 C>T, hereafter named C228T and C250T, respectively) in the TERT gene promoter have been frequently reported in various human cancers, including melanoma (71%), thyroid cancer (22-51%), bladder cancer (84.6%) and glioblastoma (83.8%).…”

Section: Dear Editorsmentioning

confidence: 99%

TERT promoter mutations predict worse survival in laryngeal cancer patients

Dang

et al. 2014

Intl Journal of Cancer

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Head and neck squamous cell cancer (HNSCC) is estimated to be the sixth most common malignant tumor worldwide. Of which, laryngeal cancer is the second most common HNSCC.1 The definite cause of laryngeal cancer is not yet determined, although some risk factors, such as tobacco and alcohol consumption, genetic and epigenetic alterations are believed to be linked with the development of this disease. 2,3Telomerase reverse transcriptase (TERT) gene, which encodes the catalytic subunit of telomerase, has been demonstrated to be up-regulated in human cancers, contributing to carcinogenesis. 4 Recently, two recurrent somatic mutations (1,295,228 C>T and 1,295,250 C>T, hereafter named C228T and C250T, respectively) in the TERT gene promoter have been frequently reported in various human cancers, including melanoma (71%), thyroid cancer (22-51%), bladder cancer (84.6%) and glioblastoma (83.8%). [5][6][7][8] In contrast, a very low frequency of these mutations has been found in certain cancers, particularly in esophageal squamous cell carcinoma (1.6%) and gastric cancer (0.7%).8-10 Importantly, these two mutations conferred a 2-to 4-fold increase in TERT transcriptional activity.5 Moreover, they have been demonstrated to be absent in benign tumors and normal subjects, implicating their potentially critical roles in human carcinogenesis. Although a previous study showed frequent TERT promoter mutations in head and neck cancers especially tongue cancer

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“…Losses of the CDKN2A gene in our cohort are consistent with this fact. The lower frequency of copy number changes in the CDKN2A gene in our cohort when compared to the frequencies of the loss of the gene function may be explained by the fact that methylation of the gene is responsible for a significant proportion of the losses, as suggested by several studies …”

Section: Discussionmentioning

confidence: 63%