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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Autor*in:	Katarzyna Kiwerska [verfasserIn] Marcin Szaumkessel [verfasserIn] Julia Paczkowska [verfasserIn] Magdalena Bodnar [verfasserIn] Ewa Byzia [verfasserIn] Ewelina Kowal [verfasserIn] Magdalena Kostrzewska-Poczekaj [verfasserIn] Joanna Janiszewska [verfasserIn] Kinga Bednarek [verfasserIn] Małgorzata Jarmuż-Szymczak [verfasserIn] Ewelina Kalinowicz [verfasserIn] Małgorzata Wierzbicka [verfasserIn] Reidar Grenman [verfasserIn] Krzysztof Szyfter [verfasserIn] Andrzej Marszałek [verfasserIn] Maciej Giefing [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Übergeordnetes Werk:	In: Scientific Reports - Nature Portfolio, 2011, 7(2017), 1, Seite 11
Übergeordnetes Werk:	volume:7 ; year:2017 ; number:1 ; pages:11

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41598-017-05857-1

Katalog-ID:	DOAJ008480931

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allfields	10.1038/s41598-017-05857-1 doi (DE-627)DOAJ008480931 (DE-599)DOAJf5cb676038514a8f9b6a3fd796b3b2b4 DE-627 ger DE-627 rakwb eng Katarzyna Kiwerska verfasserin aut Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Marcin Szaumkessel verfasserin aut Julia Paczkowska verfasserin aut Magdalena Bodnar verfasserin aut Ewa Byzia verfasserin aut Ewelina Kowal verfasserin aut Magdalena Kostrzewska-Poczekaj verfasserin aut Joanna Janiszewska verfasserin aut Kinga Bednarek verfasserin aut Małgorzata Jarmuż-Szymczak verfasserin aut Ewelina Kalinowicz verfasserin aut Małgorzata Wierzbicka verfasserin aut Reidar Grenman verfasserin aut Krzysztof Szyfter verfasserin aut Andrzej Marszałek verfasserin aut Maciej Giefing verfasserin aut In Scientific Reports Nature Portfolio, 2011 7(2017), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:7 year:2017 number:1 pages:11 https://doi.org/10.1038/s41598-017-05857-1 kostenfrei https://doaj.org/article/f5cb676038514a8f9b6a3fd796b3b2b4 kostenfrei https://doi.org/10.1038/s41598-017-05857-1 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2017 1 11
spelling	10.1038/s41598-017-05857-1 doi (DE-627)DOAJ008480931 (DE-599)DOAJf5cb676038514a8f9b6a3fd796b3b2b4 DE-627 ger DE-627 rakwb eng Katarzyna Kiwerska verfasserin aut Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Marcin Szaumkessel verfasserin aut Julia Paczkowska verfasserin aut Magdalena Bodnar verfasserin aut Ewa Byzia verfasserin aut Ewelina Kowal verfasserin aut Magdalena Kostrzewska-Poczekaj verfasserin aut Joanna Janiszewska verfasserin aut Kinga Bednarek verfasserin aut Małgorzata Jarmuż-Szymczak verfasserin aut Ewelina Kalinowicz verfasserin aut Małgorzata Wierzbicka verfasserin aut Reidar Grenman verfasserin aut Krzysztof Szyfter verfasserin aut Andrzej Marszałek verfasserin aut Maciej Giefing verfasserin aut In Scientific Reports Nature Portfolio, 2011 7(2017), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:7 year:2017 number:1 pages:11 https://doi.org/10.1038/s41598-017-05857-1 kostenfrei https://doaj.org/article/f5cb676038514a8f9b6a3fd796b3b2b4 kostenfrei https://doi.org/10.1038/s41598-017-05857-1 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2017 1 11
allfields_unstemmed	10.1038/s41598-017-05857-1 doi (DE-627)DOAJ008480931 (DE-599)DOAJf5cb676038514a8f9b6a3fd796b3b2b4 DE-627 ger DE-627 rakwb eng Katarzyna Kiwerska verfasserin aut Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Marcin Szaumkessel verfasserin aut Julia Paczkowska verfasserin aut Magdalena Bodnar verfasserin aut Ewa Byzia verfasserin aut Ewelina Kowal verfasserin aut Magdalena Kostrzewska-Poczekaj verfasserin aut Joanna Janiszewska verfasserin aut Kinga Bednarek verfasserin aut Małgorzata Jarmuż-Szymczak verfasserin aut Ewelina Kalinowicz verfasserin aut Małgorzata Wierzbicka verfasserin aut Reidar Grenman verfasserin aut Krzysztof Szyfter verfasserin aut Andrzej Marszałek verfasserin aut Maciej Giefing verfasserin aut In Scientific Reports Nature Portfolio, 2011 7(2017), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:7 year:2017 number:1 pages:11 https://doi.org/10.1038/s41598-017-05857-1 kostenfrei https://doaj.org/article/f5cb676038514a8f9b6a3fd796b3b2b4 kostenfrei https://doi.org/10.1038/s41598-017-05857-1 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2017 1 11
allfieldsGer	10.1038/s41598-017-05857-1 doi (DE-627)DOAJ008480931 (DE-599)DOAJf5cb676038514a8f9b6a3fd796b3b2b4 DE-627 ger DE-627 rakwb eng Katarzyna Kiwerska verfasserin aut Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Marcin Szaumkessel verfasserin aut Julia Paczkowska verfasserin aut Magdalena Bodnar verfasserin aut Ewa Byzia verfasserin aut Ewelina Kowal verfasserin aut Magdalena Kostrzewska-Poczekaj verfasserin aut Joanna Janiszewska verfasserin aut Kinga Bednarek verfasserin aut Małgorzata Jarmuż-Szymczak verfasserin aut Ewelina Kalinowicz verfasserin aut Małgorzata Wierzbicka verfasserin aut Reidar Grenman verfasserin aut Krzysztof Szyfter verfasserin aut Andrzej Marszałek verfasserin aut Maciej Giefing verfasserin aut In Scientific Reports Nature Portfolio, 2011 7(2017), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:7 year:2017 number:1 pages:11 https://doi.org/10.1038/s41598-017-05857-1 kostenfrei https://doaj.org/article/f5cb676038514a8f9b6a3fd796b3b2b4 kostenfrei https://doi.org/10.1038/s41598-017-05857-1 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2017 1 11
allfieldsSound	10.1038/s41598-017-05857-1 doi (DE-627)DOAJ008480931 (DE-599)DOAJf5cb676038514a8f9b6a3fd796b3b2b4 DE-627 ger DE-627 rakwb eng Katarzyna Kiwerska verfasserin aut Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Marcin Szaumkessel verfasserin aut Julia Paczkowska verfasserin aut Magdalena Bodnar verfasserin aut Ewa Byzia verfasserin aut Ewelina Kowal verfasserin aut Magdalena Kostrzewska-Poczekaj verfasserin aut Joanna Janiszewska verfasserin aut Kinga Bednarek verfasserin aut Małgorzata Jarmuż-Szymczak verfasserin aut Ewelina Kalinowicz verfasserin aut Małgorzata Wierzbicka verfasserin aut Reidar Grenman verfasserin aut Krzysztof Szyfter verfasserin aut Andrzej Marszałek verfasserin aut Maciej Giefing verfasserin aut In Scientific Reports Nature Portfolio, 2011 7(2017), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:7 year:2017 number:1 pages:11 https://doi.org/10.1038/s41598-017-05857-1 kostenfrei https://doaj.org/article/f5cb676038514a8f9b6a3fd796b3b2b4 kostenfrei https://doi.org/10.1038/s41598-017-05857-1 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2017 1 11
language	English
source	In Scientific Reports 7(2017), 1, Seite 11 volume:7 year:2017 number:1 pages:11
sourceStr	In Scientific Reports 7(2017), 1, Seite 11 volume:7 year:2017 number:1 pages:11
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Medicine R Science Q
isfreeaccess_bool	true
container_title	Scientific Reports
authorswithroles_txt_mv	Katarzyna Kiwerska @@aut@@ Marcin Szaumkessel @@aut@@ Julia Paczkowska @@aut@@ Magdalena Bodnar @@aut@@ Ewa Byzia @@aut@@ Ewelina Kowal @@aut@@ Magdalena Kostrzewska-Poczekaj @@aut@@ Joanna Janiszewska @@aut@@ Kinga Bednarek @@aut@@ Małgorzata Jarmuż-Szymczak @@aut@@ Ewelina Kalinowicz @@aut@@ Małgorzata Wierzbicka @@aut@@ Reidar Grenman @@aut@@ Krzysztof Szyfter @@aut@@ Andrzej Marszałek @@aut@@ Maciej Giefing @@aut@@
publishDateDaySort_date	2017-01-01T00:00:00Z
hierarchy_top_id	663366712
id	DOAJ008480931
language_de	englisch
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author	Katarzyna Kiwerska
spellingShingle	Katarzyna Kiwerska misc Medicine misc R misc Science misc Q Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors
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topic_title	Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors
topic	misc Medicine misc R misc Science misc Q
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title	Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors
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title_full	Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors
author_sort	Katarzyna Kiwerska
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author_browse	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
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title_sort	combined deletion and dna methylation result in silencing of fam107a gene in laryngeal tumors
title_auth	Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors
abstract	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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors
url	https://doi.org/10.1038/s41598-017-05857-1 https://doaj.org/article/f5cb676038514a8f9b6a3fd796b3b2b4 https://doaj.org/toc/2045-2322
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author2	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
author2Str	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
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Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors

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