Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors
Abstract 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 ai...
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Nature Portfolio
2017
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oai:doaj.org-article:f5cb676038514a8f9b6a3fd796b3b2b42021-12-02T15:05:49ZCombined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors10.1038/s41598-017-05857-12045-2322https://doaj.org/article/f5cb676038514a8f9b6a3fd796b3b2b42017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05857-1https://doaj.org/toc/2045-2322Abstract 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.Katarzyna KiwerskaMarcin SzaumkesselJulia PaczkowskaMagdalena BodnarEwa ByziaEwelina KowalMagdalena Kostrzewska-PoczekajJoanna JaniszewskaKinga BednarekMałgorzata Jarmuż-SzymczakEwelina KalinowiczMałgorzata WierzbickaReidar GrenmanKrzysztof SzyfterAndrzej MarszałekMaciej GiefingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Katarzyna Kiwerska Marcin Szaumkessel Julia Paczkowska Magdalena Bodnar Ewa Byzia Ewelina Kowal Magdalena Kostrzewska-Poczekaj Joanna Janiszewska Kinga Bednarek Małgorzata Jarmuż-Szymczak Ewelina Kalinowicz Małgorzata Wierzbicka Reidar Grenman Krzysztof Szyfter Andrzej Marszałek Maciej Giefing Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors |
| description |
Abstract 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 |
article |
| author |
Katarzyna Kiwerska Marcin Szaumkessel Julia Paczkowska Magdalena Bodnar Ewa Byzia Ewelina Kowal Magdalena Kostrzewska-Poczekaj Joanna Janiszewska Kinga Bednarek Małgorzata Jarmuż-Szymczak Ewelina Kalinowicz Małgorzata Wierzbicka Reidar Grenman Krzysztof Szyfter Andrzej Marszałek Maciej Giefing |
| author_facet |
Katarzyna Kiwerska Marcin Szaumkessel Julia Paczkowska Magdalena Bodnar Ewa Byzia Ewelina Kowal Magdalena Kostrzewska-Poczekaj Joanna Janiszewska Kinga Bednarek Małgorzata Jarmuż-Szymczak Ewelina Kalinowicz Małgorzata Wierzbicka Reidar Grenman Krzysztof Szyfter Andrzej Marszałek Maciej Giefing |
| author_sort |
Katarzyna Kiwerska |
| title |
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_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_sort |
combined deletion and dna methylation result in silencing of fam107a gene in laryngeal tumors |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/f5cb676038514a8f9b6a3fd796b3b2b4 |
| work_keys_str_mv |
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| _version_ |
1718388744445231104 |