Bioinformatics for High‐Throughput Toxico‐Epigenomics Studies

Sartor, Maureen A.; Dolinoy, Dana C.; Rozek, Laura S.; Omenn, Gilbert S.

doi:10.1002/9781118349045.ch28

Cited by 3 publications

(3 citation statements)

References 93 publications

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“…More likely factors for malignant progression in the Cancer Genetics HPV-positive group include the accumulation of confined chromosomal alterations, such as extra copies of chromosome 3q found in HPV-positive uterine cervical cancers and TSCC, [39][40][41] deletion of 16q, 40,41 and/or modification of the methylation status of the host cell DNA. 42,43 In addition, molecular alterations underlying lymphangiogenesis and epithelial mesenchymal transition might contribute to malignant tumor progression in these cases. 44,45 Because most HPV-positive TSCCs are genomically stable, it could be expected that also their associated precursor lesions show this feature.…”

Section: Discussionmentioning

confidence: 99%

Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis

Mooren

Kremer

Claessen

et al. 2012

Intl Journal of Cancer

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Tonsillar squamous cell carcinoma (TSCC) is frequently associated with human papillomavirus (HPV) and chromosome instability. Data from cellular model systems are, however, controversial concerning a relation between HPV and chromosome instability development. Here we studied this association in 77 primary TSCC with known clinical outcome and cell cycle protein expression profiles. Thirty‐two tumors (42%) showed HPV16‐integration. All 77 cases were analyzed by fluorescence in situ hybridization using chromosome 1‐ and 7‐specific centromere DNA probes to detect chromosome instability, indicated by the presence of chromosome imbalances and/or polyploidization for these chromosomes. In addition, eight HPV‐positive dysplasias, seven of which were adjacent to a carcinoma, were analyzed. Disomy for chromosome 1 and 7 was present in 29 out of 77 TSCC (38%), of which 19 were HPV16‐positive (p = 0.002). Aneusomy was observed in the remaining 48 TSCC, of which 13 were HPV‐positive. Aneusomies correlated significantly with tobacco‐ and alcohol consumption (p = 0.001 and p = 0.016, respectively) and a higher T‐stage (p = 0.018). Both HPV‐positivity and chromosome disomy were significantly associated with a favorable disease‐free survival (p = 0.001 and p = 0.025, respectively). Particularly in the HPV16‐positive group chromosome instability is a very strong indicator for an unfavorable prognosis (p = 0.032). In the dysplasias an identical HPV and chromosome copy number status was identified as in the adjacent tumors. We conclude that HPV‐positive TSCC and their precursor lesions are more often genetically stable than HPV‐negative lesions and that these tumors are associated with a favorable prognosis. Chromosome instability is an indicator for unfavorable prognosis, particularly in the HPV‐positive patient group.

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Section: Discussionmentioning

confidence: 99%

Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis

Mooren

Kremer

Claessen

et al. 2012

Intl Journal of Cancer

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“…As a result, it's critical to explore current trends, possible uses, and anticipated constraints that researchers are encountering when incorporating epigenetic data into human health assessment models. Toxicoepigenomics has the potential to meet critical demands in both science and applied toxicology [9].…”

Section: Current Trends In Toxicoepigenomics Researchmentioning

confidence: 99%

Current trends in toxicoepigenomics research, limitations and future perspective

Khan¹,

Atta²,

Niaz

2021

J. Bashir Inst. Health Sci.

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Toxicoepigenomics is new field emerged from the combination of toxicology and epigenetics. It is defined as the heritable changes in the gene activity induced by exposure to environment and toxicant substances such as heavy metals without any alterations in the existing nucleotide sequence. Research studies show that epigenetics plays important role in the development of certain human diseases such as diabetes and cancer. Hence toxicoepigenomics has evolved as an important new area in toxicology research. In toxicoepigenomics targeting DNA methylation alteration as a tool to identify the underlying causes of disease development exists as important trend in the current research design, but this aspect of toxicoepigenomics has been evaluated extensively. New mechanisms such as microRNA (miRNA) dysregulations need to be considered for future research work. Furthermore, it is important to consider different study designs such as the application of parallel in vitro and in vivo studies. This might be an interesting aspect of toxicoepigenomics research and will enable researchers to fill the gap in the existing research designs.

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“…We applied one such tool, LRpath, to identify common pathways dysregulated via DNA methylation across cancer types (44). For a review of the available sequencing technologies and bioinformatics methods for performing, analyzing, and interpreting epigenomics studies, as well as integrative approaches for understanding the epigenetics in the context of the genome and transcriptome, see Sartor et al (82). …”

Section: Introductionmentioning

confidence: 99%

Epigenetics: Relevance and Implications for Public Health

Rozek

Dolinoy

Sartor

et al. 2014

Annu. Rev. Public Health

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Improved understanding of the multilayer regulation of the human genome has led to a greater appreciation of environmental, nutritional, and epigenetic risk factors for human disease. Chromatin remodeling, histone tail modifications, and DNA methylation are dynamic epigenetic changes responsive to external stimuli. Careful interpretation can provide insights for actionable public health through collaboration between population and basic scientists and through integration of multiple data sources. We review key findings in environmental epigenetics both in human population studies and in animal models, and discuss the implications of these results for risk assessment and public health protection. To ultimately succeed in identifying epigenetic mechanisms leading to complex phenotypes and disease, researchers must integrate the various animal models, human clinical approaches, and human population approaches while paying attention to life-stage sensitivity, to generate effective prescriptions for human health evaluation and disease prevention.

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Bioinformatics for High‐Throughput Toxico‐Epigenomics Studies

Cited by 3 publications

References 93 publications

Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis

Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis

Current trends in toxicoepigenomics research, limitations and future perspective

Epigenetics: Relevance and Implications for Public Health

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