Analysis of DNA methylation and gene expression in radiation-resistant head and neck tumors

Chen, Xiaofei; Lang, Liang; Mims, Jade; Punska, Elizabeth C.; Williams, Kristin E.; Zhao, Weiling; Arcaro, Kathleen F.; Tsang, Allen W.; Zhou, Xiaobo; Furdui, Cristina M.

doi:10.1080/15592294.2015.1048953

Cited by 68 publications

(55 citation statements)

References 52 publications

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“…For most of the methylomics driven studies of HNSCC [183, 185, 188, 189], few cases were analyzed (particularly for HPV+ cases) and additional work is needed to better understanding and interpret the various methylation patterns. How methylomics data is going to be integrated into clinical practice for HNSCC remains to be seen, although prognostic and diagnostic potential of such information is apparent in some cancer types [181, 185, 190]. No DNA methylation markers for HNSCC have been accepted for clinical use to date [185].…”

Section: Introductionmentioning

confidence: 99%

Genomic insights into head and neck cancer

Beck

Golemis

2016

Cancers Head Neck

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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is frequently impervious to curative treatment efforts. Similar to other cancers associated with prolonged exposure to carcinogens, HNSCCs often have a high burden of mutations, contributing to substantial inter- and intra-tumor heterogeneity. The heterogeneity of this malignancy is further increased by the rising rate of human papillomavirus (HPV)-associated (HPV+) HNSCC, which defines an etiological subtype significantly different from the more common tobacco and alcohol associated HPV-negative (HPV−) HNSCC. Since 2011, application of large scale genome sequencing projects by The Cancer Genome Atlas (TCGA) network and other groups have established extensive datasets to characterize HPV− and HPV+ HNSCC, providing a foundation for advanced molecular diagnoses, identification of potential biomarkers, and therapeutic insights. Some genomic lesions are now appreciated as widely dispersed. For example, HPV− HNSCC characteristically inactivates the cell cycle suppressors TP53 (p53) and CDKN2A (p16), and often amplifies CCND1 (cyclin D), which phosphorylates RB1 to promote cell cycle progression from G1 to S. By contrast, HPV+ HNSCC expresses viral oncogenes E6 and E7, which inhibit TP53 and RB1, and activates the cell cycle regulator E2F1. Frequent activating mutations in PIK3CA and inactivating mutations in NOTCH1 are seen in both subtypes of HNSCC, emphasizing the importance of these pathways. Studies of large patient cohorts have also begun to identify less common genetic alterations, predominantly found in HPV− tumors, which suggest new mechanisms relevant to disease pathogenesis. Targets of these alterations including AJUBA and FAT1, both involved in the regulation of NOTCH/CTNNB1 signaling. Genes involved in oxidative stress, particularly CUL3, KEAP1 and NFE2L2, strongly associated with smoking, have also been identified, and are less well understood mechanistically. Application of sophisticated data-mining approaches, integrating genomic information with profiles of tumor methylation and gene expression, have helped to further yield insights, and in some cases suggest additional approaches to stratify patients for clinical treatment. We here discuss some recent insights built on TCGA and other genomic foundations.

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Section: Introductionmentioning

confidence: 99%

Genomic insights into head and neck cancer

Beck

Golemis

2016

Cancers Head Neck

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“…To explore the mechanism of resistance to head and neck squamous cell cancer (HNSCC) radiotherapy, Chen et al3 analyzed the DNA methylation of cyclin D2 (CCND2) in 2 counterpart HNSCC cell lines. This cyclin forms a complex with cyclin‐dependent kinase 4 (CDK4) or cyclin‐dependent kinase 6 (CDK6) and acts as a regulatory subunit of the complex, whose activity is essential for cell cycle G1/S transition 30…”

Section: Radio‐sensitivity and Dna Methylation Of Cell Cycle‐relatedmentioning

confidence: 99%

“…However, parts of patients with above tumors are resistant to irradiation or some initially sensitive patients develop into irradiation resistance. Hence, irradiation resistance is 1 of the major obstacles that leads to loco‐regional recurrence of malignant tumors during treatment 2, 3, 4, 5, 6…”

Section: Introductionmentioning

confidence: 99%

The pivotal role of DNA methylation in the radio‐sensitivity of tumor radiotherapy

et al. 2018

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Radiotherapy is an important modality for treatment of carcinomas; however, radio‐resistance is still a difficult problem. Aberrant epigenetic alterations play an important role in cancer development. Among epigenetic parameters, DNA methylation has arguably attracted the most attention in the radio‐resistance process. To determine the role of DNA methylation in radiation resistance, several studies were conducted. We summarized previous studies on the role of DNA methylation in radiotherapy. We observed this significant role of DNA methylation in genes related to DNA repair, cell proliferation, cell cycle process, and re‐oxygenation. Furtherly, we also conclude the predictive effect of DNA methylation on tumor radio‐sensitivity and the using of DNA methyltransferase inhibitors in clinical practice. DNA methylation plays a pivotal role in the radio‐sensitivity of tumor radio‐therapy. While hyper‐methylation or hypo‐methylation of genes is related to gene functions.

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“…Treatment resistance is, however, a common occurrence and - over the past 10 years - the role of DNA methylation in the efficacy/inefficacy of each of these treatments has been the focus of considerable investigation. DNA methylation differences were observed between radio-sensitive and radio-resistant cell lines 17,18 . Specific and reproducible changes in DNA methylation have been observed in cells surviving radiation 17 .…”

Section: Therapeutic Sensitivity/resistancementioning

confidence: 99%

“…DNA methylation differences were observed between radio-sensitive and radio-resistant cell lines 17,18 . Specific and reproducible changes in DNA methylation have been observed in cells surviving radiation 17 . Most importantly, however, inhibition of DNA methylases with 5-aza-cytidine sensitizes a number of radiation resistant cancers to radiation, demonstrating that DNA methylation plays an important role in radio-resistance in the clinic.…”

Section: Therapeutic Sensitivity/resistancementioning

confidence: 99%

The Roles of DNA Methylation in the Stages of Cancer

McMahon¹,

Karunasena²,

Ahuja³

2017

Cancer J

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Next year will mark 60 years since Dr. Leslie Foulds outlined his hypothesis that cancer is “a dynamic process advancing through stages that are qualitatively different,”1 leading the way to our view of cancer progression as we know it today2. Our understanding of the mechanisms of these stages have been continuously evolving this past half-century and there has always been an active discussion of the roles of both genetic or epigenetic changes in directing this progression. In this review, we will focus on the roles one particular epigenetic mark - DNA methylation - plays in these various “discontinuous” stages of cancer. Understanding these steps not only gives us a better picture of how this fascinating biological process operates, but opens the doors to new prognostic biomarkers and therapies against these malignancies.

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Analysis of DNA methylation and gene expression in radiation-resistant head and neck tumors

Cited by 68 publications

References 52 publications

Genomic insights into head and neck cancer

Genomic insights into head and neck cancer

The pivotal role of DNA methylation in the radio‐sensitivity of tumor radiotherapy

The Roles of DNA Methylation in the Stages of Cancer

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