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Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC
Over a half million new cases of Head and Neck Squamous Cell Carcinoma (HNSCC) are diagnosed annually worldwide, however, 5 year overall survival is only 50% for HNSCC patients. Recently, high throughput technologies have accelerated the genome-wide characterization of HNSCC. However, comprehensive...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362490/ https://www.ncbi.nlm.nih.gov/pubmed/28146432 http://dx.doi.org/10.18632/oncotarget.14856 |
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author | Gaykalova, Daria A. Zizkova, Veronika Guo, Theresa Tiscareno, Ilse Wei, Yingying Vatapalli, Rajita Hennessey, Patrick T. Ahn, Julie Danilova, Ludmila Khan, Zubair Bishop, Justin A. Silvio Gutkind, J. Koch, Wayne M. Westra, William H. Fertig, Elana J. Ochs, Michael F. Califano, Joseph A. |
author_facet | Gaykalova, Daria A. Zizkova, Veronika Guo, Theresa Tiscareno, Ilse Wei, Yingying Vatapalli, Rajita Hennessey, Patrick T. Ahn, Julie Danilova, Ludmila Khan, Zubair Bishop, Justin A. Silvio Gutkind, J. Koch, Wayne M. Westra, William H. Fertig, Elana J. Ochs, Michael F. Califano, Joseph A. |
author_sort | Gaykalova, Daria A. |
collection | PubMed |
description | Over a half million new cases of Head and Neck Squamous Cell Carcinoma (HNSCC) are diagnosed annually worldwide, however, 5 year overall survival is only 50% for HNSCC patients. Recently, high throughput technologies have accelerated the genome-wide characterization of HNSCC. However, comprehensive pipelines with statistical algorithms that account for HNSCC biology and perform independent confirmatory and functional validation of candidates are needed to identify the most biologically relevant genes. We applied outlier statistics to high throughput gene expression data, and identified 76 top-scoring candidates with significant differential expression in tumors compared to normal tissues. We identified 15 epigenetically regulated candidates by focusing on a subset of the genes with a negative correlation between gene expression and promoter methylation. Differential expression and methylation of 3 selected candidates (BANK1, BIN2, and DTX1) were confirmed in an independent HNSCC cohorts from Johns Hopkins and TCGA (The Cancer Genome Atlas). We further performed functional evaluation of NOTCH regulator, DTX1, which was downregulated by promoter hypermethylation in tumors, and demonstrated that decreased expression of DTX1 in HNSCC tumors maybe associated with NOTCH pathway activation and increased migration potential. |
format | Online Article Text |
id | pubmed-5362490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53624902017-04-24 Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC Gaykalova, Daria A. Zizkova, Veronika Guo, Theresa Tiscareno, Ilse Wei, Yingying Vatapalli, Rajita Hennessey, Patrick T. Ahn, Julie Danilova, Ludmila Khan, Zubair Bishop, Justin A. Silvio Gutkind, J. Koch, Wayne M. Westra, William H. Fertig, Elana J. Ochs, Michael F. Califano, Joseph A. Oncotarget Research Paper Over a half million new cases of Head and Neck Squamous Cell Carcinoma (HNSCC) are diagnosed annually worldwide, however, 5 year overall survival is only 50% for HNSCC patients. Recently, high throughput technologies have accelerated the genome-wide characterization of HNSCC. However, comprehensive pipelines with statistical algorithms that account for HNSCC biology and perform independent confirmatory and functional validation of candidates are needed to identify the most biologically relevant genes. We applied outlier statistics to high throughput gene expression data, and identified 76 top-scoring candidates with significant differential expression in tumors compared to normal tissues. We identified 15 epigenetically regulated candidates by focusing on a subset of the genes with a negative correlation between gene expression and promoter methylation. Differential expression and methylation of 3 selected candidates (BANK1, BIN2, and DTX1) were confirmed in an independent HNSCC cohorts from Johns Hopkins and TCGA (The Cancer Genome Atlas). We further performed functional evaluation of NOTCH regulator, DTX1, which was downregulated by promoter hypermethylation in tumors, and demonstrated that decreased expression of DTX1 in HNSCC tumors maybe associated with NOTCH pathway activation and increased migration potential. Impact Journals LLC 2017-01-27 /pmc/articles/PMC5362490/ /pubmed/28146432 http://dx.doi.org/10.18632/oncotarget.14856 Text en Copyright: © 2017 Gaykalova et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Gaykalova, Daria A. Zizkova, Veronika Guo, Theresa Tiscareno, Ilse Wei, Yingying Vatapalli, Rajita Hennessey, Patrick T. Ahn, Julie Danilova, Ludmila Khan, Zubair Bishop, Justin A. Silvio Gutkind, J. Koch, Wayne M. Westra, William H. Fertig, Elana J. Ochs, Michael F. Califano, Joseph A. Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC |
title | Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC |
title_full | Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC |
title_fullStr | Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC |
title_full_unstemmed | Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC |
title_short | Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC |
title_sort | integrative computational analysis of transcriptional and epigenetic alterations implicates dtx1 as a putative tumor suppressor gene in hnscc |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362490/ https://www.ncbi.nlm.nih.gov/pubmed/28146432 http://dx.doi.org/10.18632/oncotarget.14856 |
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