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Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors
Larynx squamous cell carcinoma (LSCC) is characterized by complex genotypes, with numerous abnormalities in various genes. Despite the progress in diagnosis and treatment of this disease, 5-year survival rates remain unsatisfactory. Therefore, the extended studies are conducted, with the aim to find...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511162/ https://www.ncbi.nlm.nih.gov/pubmed/28710449 http://dx.doi.org/10.1038/s41598-017-05857-1 |
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author | Kiwerska, Katarzyna Szaumkessel, Marcin Paczkowska, Julia Bodnar, Magdalena Byzia, Ewa Kowal, Ewelina Kostrzewska-Poczekaj, Magdalena Janiszewska, Joanna Bednarek, Kinga Jarmuż-Szymczak, Małgorzata Kalinowicz, Ewelina Wierzbicka, Małgorzata Grenman, Reidar Szyfter, Krzysztof Marszałek, Andrzej Giefing, Maciej |
author_facet | Kiwerska, Katarzyna Szaumkessel, Marcin Paczkowska, Julia Bodnar, Magdalena Byzia, Ewa Kowal, Ewelina Kostrzewska-Poczekaj, Magdalena Janiszewska, Joanna Bednarek, Kinga Jarmuż-Szymczak, Małgorzata Kalinowicz, Ewelina Wierzbicka, Małgorzata Grenman, Reidar Szyfter, Krzysztof Marszałek, Andrzej Giefing, Maciej |
author_sort | Kiwerska, Katarzyna |
collection | PubMed |
description | Larynx squamous cell carcinoma (LSCC) is characterized by complex genotypes, with numerous abnormalities in various genes. Despite the progress in diagnosis and treatment of this disease, 5-year survival rates remain unsatisfactory. Therefore, the extended studies are conducted, with the aim to find genes, potentially implicated in this cancer. In this study, we focus on the FAM107A (3p14.3) gene, since we found its significantly reduced expression in LSCC by microarray profiling (Affymetrix U133 Plus 2.0 array). By RT-PCR we have confirmed complete FAM107A downregulation in laryngeal cancer cell lines (15/15) and primary tumors (21/21) and this finding was further supported by FAM107A protein immunohistochemistry (15/15). We further demonstrate that a combined two hit mechanism including loss of 3p and hypermethylation of FAM107A promoter region (in 9/15 cell lines (p < 0.0001) and in 15/21 primary tumors (p < 0.0001)) prevails in the gene transcriptional loss. As a proof of principle, we show that Decitabine - a hypomethylating agent – restores FAM107A expression (5 to 6 fold increase) in the UT-SCC-29 cell line, characterized by high DNA methylation. Therefore, we report the recurrent inactivation of FAM107A in LSCC, what may suggest that the gene is a promising tumor suppressor candidate involved in LSCC development. |
format | Online Article Text |
id | pubmed-5511162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55111622017-07-17 Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors Kiwerska, Katarzyna Szaumkessel, Marcin Paczkowska, Julia Bodnar, Magdalena Byzia, Ewa Kowal, Ewelina Kostrzewska-Poczekaj, Magdalena Janiszewska, Joanna Bednarek, Kinga Jarmuż-Szymczak, Małgorzata Kalinowicz, Ewelina Wierzbicka, Małgorzata Grenman, Reidar Szyfter, Krzysztof Marszałek, Andrzej Giefing, Maciej Sci Rep Article Larynx squamous cell carcinoma (LSCC) is characterized by complex genotypes, with numerous abnormalities in various genes. Despite the progress in diagnosis and treatment of this disease, 5-year survival rates remain unsatisfactory. Therefore, the extended studies are conducted, with the aim to find genes, potentially implicated in this cancer. In this study, we focus on the FAM107A (3p14.3) gene, since we found its significantly reduced expression in LSCC by microarray profiling (Affymetrix U133 Plus 2.0 array). By RT-PCR we have confirmed complete FAM107A downregulation in laryngeal cancer cell lines (15/15) and primary tumors (21/21) and this finding was further supported by FAM107A protein immunohistochemistry (15/15). We further demonstrate that a combined two hit mechanism including loss of 3p and hypermethylation of FAM107A promoter region (in 9/15 cell lines (p < 0.0001) and in 15/21 primary tumors (p < 0.0001)) prevails in the gene transcriptional loss. As a proof of principle, we show that Decitabine - a hypomethylating agent – restores FAM107A expression (5 to 6 fold increase) in the UT-SCC-29 cell line, characterized by high DNA methylation. Therefore, we report the recurrent inactivation of FAM107A in LSCC, what may suggest that the gene is a promising tumor suppressor candidate involved in LSCC development. Nature Publishing Group UK 2017-07-14 /pmc/articles/PMC5511162/ /pubmed/28710449 http://dx.doi.org/10.1038/s41598-017-05857-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kiwerska, Katarzyna Szaumkessel, Marcin Paczkowska, Julia Bodnar, Magdalena Byzia, Ewa Kowal, Ewelina Kostrzewska-Poczekaj, Magdalena Janiszewska, Joanna Bednarek, Kinga Jarmuż-Szymczak, Małgorzata Kalinowicz, Ewelina Wierzbicka, Małgorzata Grenman, Reidar Szyfter, Krzysztof Marszałek, Andrzej Giefing, Maciej Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors |
title | Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors |
title_full | Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors |
title_fullStr | Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors |
title_full_unstemmed | Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors |
title_short | Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors |
title_sort | combined deletion and dna methylation result in silencing of fam107a gene in laryngeal tumors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511162/ https://www.ncbi.nlm.nih.gov/pubmed/28710449 http://dx.doi.org/10.1038/s41598-017-05857-1 |
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