Emerging role of mutations in epigenetic regulators including MLL2 derived from The Cancer Genome Atlas for cervical cancer
Background Cervical cancer is the second most common cause of cancer deaths in women worldwide. The aim of this study is to exploit novel pathogenic genes in cervical carcinogenesis. Method The somatic mutations from 194 patients with cervical cancer were obtained from the Cancer Genome Atlas (TCGA)...
Ausführliche Beschreibung
Autor*in: |
Li, Xia [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2017 |
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Anmerkung: |
© The Author(s). 2017 |
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Übergeordnetes Werk: |
Enthalten in: BMC cancer - London : BioMed Central, 2001, 17(2017), 1 vom: 08. Apr. |
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Übergeordnetes Werk: |
volume:17 ; year:2017 ; number:1 ; day:08 ; month:04 |
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DOI / URN: |
10.1186/s12885-017-3257-x |
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SPR02768623X |
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520 | |a Background Cervical cancer is the second most common cause of cancer deaths in women worldwide. The aim of this study is to exploit novel pathogenic genes in cervical carcinogenesis. Method The somatic mutations from 194 patients with cervical cancer were obtained from the Cancer Genome Atlas (TCGA) publically accessible exome-sequencing database. We investigated mutated gene enrichment in the 12 cancer core pathways and predicted possible post-translational modifications. Additionally, we predicted the impact of mutations by scores quantifying the deleterious effects of the mutations. We also examined the immunogenicity of the mutations based on the mutant peptides’ strong binding with major histocompatibility complex class I molecules (MHC-I). The Kaplan-Meier method was used for the survival analysis. Results We observed that the chromatin modification pathway was significantly mutated across all clinical stages. Among the mutated genes involved in this pathway, we observed that the histone modification regulators were primarily mutated. Interestingly, of the 197 mutations in the 26 epigenetic regulators in this pathway, 25 missense mutations in 13 genes were predicted in or around the phosphorylation sites. Only mutations in the histone methyltransferase MLL2 exhibited poor survival. Compared to other mutations in MLL2 mutant patients, we noticed that the mutational scores prioritized mutations in MLL2, which indicates that it is more likely to have deleterious effects to the human genome. Around half of all of the mutations were found to bind strongly to MHC-I, suggesting that patients are likely to benefit from immunotherapy. Conclusions Our results highlight the emerging role of mutations in epigenetic regulators, particularly MLL2, in cervical carcinogenesis, which suggests a potential disruption of histone modifications. These data have implications for further investigation of the mechanism of epigenetic dysregulation and for treatment of cervical cancer. | ||
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10.1186/s12885-017-3257-x doi (DE-627)SPR02768623X (SPR)s12885-017-3257-x-e DE-627 ger DE-627 rakwb eng Li, Xia verfasserin aut Emerging role of mutations in epigenetic regulators including MLL2 derived from The Cancer Genome Atlas for cervical cancer 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Cervical cancer is the second most common cause of cancer deaths in women worldwide. The aim of this study is to exploit novel pathogenic genes in cervical carcinogenesis. Method The somatic mutations from 194 patients with cervical cancer were obtained from the Cancer Genome Atlas (TCGA) publically accessible exome-sequencing database. We investigated mutated gene enrichment in the 12 cancer core pathways and predicted possible post-translational modifications. Additionally, we predicted the impact of mutations by scores quantifying the deleterious effects of the mutations. We also examined the immunogenicity of the mutations based on the mutant peptides’ strong binding with major histocompatibility complex class I molecules (MHC-I). The Kaplan-Meier method was used for the survival analysis. Results We observed that the chromatin modification pathway was significantly mutated across all clinical stages. Among the mutated genes involved in this pathway, we observed that the histone modification regulators were primarily mutated. Interestingly, of the 197 mutations in the 26 epigenetic regulators in this pathway, 25 missense mutations in 13 genes were predicted in or around the phosphorylation sites. Only mutations in the histone methyltransferase MLL2 exhibited poor survival. Compared to other mutations in MLL2 mutant patients, we noticed that the mutational scores prioritized mutations in MLL2, which indicates that it is more likely to have deleterious effects to the human genome. Around half of all of the mutations were found to bind strongly to MHC-I, suggesting that patients are likely to benefit from immunotherapy. Conclusions Our results highlight the emerging role of mutations in epigenetic regulators, particularly MLL2, in cervical carcinogenesis, which suggests a potential disruption of histone modifications. These data have implications for further investigation of the mechanism of epigenetic dysregulation and for treatment of cervical cancer. Mutation (dpeaa)DE-He213 TCGA (dpeaa)DE-He213 Epigenetic regulator (dpeaa)DE-He213 Cervical cancer (dpeaa)DE-He213 Enthalten in BMC cancer London : BioMed Central, 2001 17(2017), 1 vom: 08. Apr. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:17 year:2017 number:1 day:08 month:04 https://dx.doi.org/10.1186/s12885-017-3257-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2017 1 08 04 |
spelling |
10.1186/s12885-017-3257-x doi (DE-627)SPR02768623X (SPR)s12885-017-3257-x-e DE-627 ger DE-627 rakwb eng Li, Xia verfasserin aut Emerging role of mutations in epigenetic regulators including MLL2 derived from The Cancer Genome Atlas for cervical cancer 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Cervical cancer is the second most common cause of cancer deaths in women worldwide. The aim of this study is to exploit novel pathogenic genes in cervical carcinogenesis. Method The somatic mutations from 194 patients with cervical cancer were obtained from the Cancer Genome Atlas (TCGA) publically accessible exome-sequencing database. We investigated mutated gene enrichment in the 12 cancer core pathways and predicted possible post-translational modifications. Additionally, we predicted the impact of mutations by scores quantifying the deleterious effects of the mutations. We also examined the immunogenicity of the mutations based on the mutant peptides’ strong binding with major histocompatibility complex class I molecules (MHC-I). The Kaplan-Meier method was used for the survival analysis. Results We observed that the chromatin modification pathway was significantly mutated across all clinical stages. Among the mutated genes involved in this pathway, we observed that the histone modification regulators were primarily mutated. Interestingly, of the 197 mutations in the 26 epigenetic regulators in this pathway, 25 missense mutations in 13 genes were predicted in or around the phosphorylation sites. Only mutations in the histone methyltransferase MLL2 exhibited poor survival. Compared to other mutations in MLL2 mutant patients, we noticed that the mutational scores prioritized mutations in MLL2, which indicates that it is more likely to have deleterious effects to the human genome. Around half of all of the mutations were found to bind strongly to MHC-I, suggesting that patients are likely to benefit from immunotherapy. Conclusions Our results highlight the emerging role of mutations in epigenetic regulators, particularly MLL2, in cervical carcinogenesis, which suggests a potential disruption of histone modifications. These data have implications for further investigation of the mechanism of epigenetic dysregulation and for treatment of cervical cancer. Mutation (dpeaa)DE-He213 TCGA (dpeaa)DE-He213 Epigenetic regulator (dpeaa)DE-He213 Cervical cancer (dpeaa)DE-He213 Enthalten in BMC cancer London : BioMed Central, 2001 17(2017), 1 vom: 08. Apr. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:17 year:2017 number:1 day:08 month:04 https://dx.doi.org/10.1186/s12885-017-3257-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2017 1 08 04 |
allfields_unstemmed |
10.1186/s12885-017-3257-x doi (DE-627)SPR02768623X (SPR)s12885-017-3257-x-e DE-627 ger DE-627 rakwb eng Li, Xia verfasserin aut Emerging role of mutations in epigenetic regulators including MLL2 derived from The Cancer Genome Atlas for cervical cancer 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Cervical cancer is the second most common cause of cancer deaths in women worldwide. The aim of this study is to exploit novel pathogenic genes in cervical carcinogenesis. Method The somatic mutations from 194 patients with cervical cancer were obtained from the Cancer Genome Atlas (TCGA) publically accessible exome-sequencing database. We investigated mutated gene enrichment in the 12 cancer core pathways and predicted possible post-translational modifications. Additionally, we predicted the impact of mutations by scores quantifying the deleterious effects of the mutations. We also examined the immunogenicity of the mutations based on the mutant peptides’ strong binding with major histocompatibility complex class I molecules (MHC-I). The Kaplan-Meier method was used for the survival analysis. Results We observed that the chromatin modification pathway was significantly mutated across all clinical stages. Among the mutated genes involved in this pathway, we observed that the histone modification regulators were primarily mutated. Interestingly, of the 197 mutations in the 26 epigenetic regulators in this pathway, 25 missense mutations in 13 genes were predicted in or around the phosphorylation sites. Only mutations in the histone methyltransferase MLL2 exhibited poor survival. Compared to other mutations in MLL2 mutant patients, we noticed that the mutational scores prioritized mutations in MLL2, which indicates that it is more likely to have deleterious effects to the human genome. Around half of all of the mutations were found to bind strongly to MHC-I, suggesting that patients are likely to benefit from immunotherapy. Conclusions Our results highlight the emerging role of mutations in epigenetic regulators, particularly MLL2, in cervical carcinogenesis, which suggests a potential disruption of histone modifications. These data have implications for further investigation of the mechanism of epigenetic dysregulation and for treatment of cervical cancer. Mutation (dpeaa)DE-He213 TCGA (dpeaa)DE-He213 Epigenetic regulator (dpeaa)DE-He213 Cervical cancer (dpeaa)DE-He213 Enthalten in BMC cancer London : BioMed Central, 2001 17(2017), 1 vom: 08. Apr. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:17 year:2017 number:1 day:08 month:04 https://dx.doi.org/10.1186/s12885-017-3257-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2017 1 08 04 |
allfieldsGer |
10.1186/s12885-017-3257-x doi (DE-627)SPR02768623X (SPR)s12885-017-3257-x-e DE-627 ger DE-627 rakwb eng Li, Xia verfasserin aut Emerging role of mutations in epigenetic regulators including MLL2 derived from The Cancer Genome Atlas for cervical cancer 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Cervical cancer is the second most common cause of cancer deaths in women worldwide. The aim of this study is to exploit novel pathogenic genes in cervical carcinogenesis. Method The somatic mutations from 194 patients with cervical cancer were obtained from the Cancer Genome Atlas (TCGA) publically accessible exome-sequencing database. We investigated mutated gene enrichment in the 12 cancer core pathways and predicted possible post-translational modifications. Additionally, we predicted the impact of mutations by scores quantifying the deleterious effects of the mutations. We also examined the immunogenicity of the mutations based on the mutant peptides’ strong binding with major histocompatibility complex class I molecules (MHC-I). The Kaplan-Meier method was used for the survival analysis. Results We observed that the chromatin modification pathway was significantly mutated across all clinical stages. Among the mutated genes involved in this pathway, we observed that the histone modification regulators were primarily mutated. Interestingly, of the 197 mutations in the 26 epigenetic regulators in this pathway, 25 missense mutations in 13 genes were predicted in or around the phosphorylation sites. Only mutations in the histone methyltransferase MLL2 exhibited poor survival. Compared to other mutations in MLL2 mutant patients, we noticed that the mutational scores prioritized mutations in MLL2, which indicates that it is more likely to have deleterious effects to the human genome. Around half of all of the mutations were found to bind strongly to MHC-I, suggesting that patients are likely to benefit from immunotherapy. Conclusions Our results highlight the emerging role of mutations in epigenetic regulators, particularly MLL2, in cervical carcinogenesis, which suggests a potential disruption of histone modifications. These data have implications for further investigation of the mechanism of epigenetic dysregulation and for treatment of cervical cancer. Mutation (dpeaa)DE-He213 TCGA (dpeaa)DE-He213 Epigenetic regulator (dpeaa)DE-He213 Cervical cancer (dpeaa)DE-He213 Enthalten in BMC cancer London : BioMed Central, 2001 17(2017), 1 vom: 08. Apr. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:17 year:2017 number:1 day:08 month:04 https://dx.doi.org/10.1186/s12885-017-3257-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2017 1 08 04 |
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10.1186/s12885-017-3257-x doi (DE-627)SPR02768623X (SPR)s12885-017-3257-x-e DE-627 ger DE-627 rakwb eng Li, Xia verfasserin aut Emerging role of mutations in epigenetic regulators including MLL2 derived from The Cancer Genome Atlas for cervical cancer 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Cervical cancer is the second most common cause of cancer deaths in women worldwide. The aim of this study is to exploit novel pathogenic genes in cervical carcinogenesis. Method The somatic mutations from 194 patients with cervical cancer were obtained from the Cancer Genome Atlas (TCGA) publically accessible exome-sequencing database. We investigated mutated gene enrichment in the 12 cancer core pathways and predicted possible post-translational modifications. Additionally, we predicted the impact of mutations by scores quantifying the deleterious effects of the mutations. We also examined the immunogenicity of the mutations based on the mutant peptides’ strong binding with major histocompatibility complex class I molecules (MHC-I). The Kaplan-Meier method was used for the survival analysis. Results We observed that the chromatin modification pathway was significantly mutated across all clinical stages. Among the mutated genes involved in this pathway, we observed that the histone modification regulators were primarily mutated. Interestingly, of the 197 mutations in the 26 epigenetic regulators in this pathway, 25 missense mutations in 13 genes were predicted in or around the phosphorylation sites. Only mutations in the histone methyltransferase MLL2 exhibited poor survival. Compared to other mutations in MLL2 mutant patients, we noticed that the mutational scores prioritized mutations in MLL2, which indicates that it is more likely to have deleterious effects to the human genome. Around half of all of the mutations were found to bind strongly to MHC-I, suggesting that patients are likely to benefit from immunotherapy. Conclusions Our results highlight the emerging role of mutations in epigenetic regulators, particularly MLL2, in cervical carcinogenesis, which suggests a potential disruption of histone modifications. These data have implications for further investigation of the mechanism of epigenetic dysregulation and for treatment of cervical cancer. Mutation (dpeaa)DE-He213 TCGA (dpeaa)DE-He213 Epigenetic regulator (dpeaa)DE-He213 Cervical cancer (dpeaa)DE-He213 Enthalten in BMC cancer London : BioMed Central, 2001 17(2017), 1 vom: 08. Apr. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:17 year:2017 number:1 day:08 month:04 https://dx.doi.org/10.1186/s12885-017-3257-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2017 1 08 04 |
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Emerging role of mutations in epigenetic regulators including MLL2 derived from The Cancer Genome Atlas for cervical cancer |
abstract |
Background Cervical cancer is the second most common cause of cancer deaths in women worldwide. The aim of this study is to exploit novel pathogenic genes in cervical carcinogenesis. Method The somatic mutations from 194 patients with cervical cancer were obtained from the Cancer Genome Atlas (TCGA) publically accessible exome-sequencing database. We investigated mutated gene enrichment in the 12 cancer core pathways and predicted possible post-translational modifications. Additionally, we predicted the impact of mutations by scores quantifying the deleterious effects of the mutations. We also examined the immunogenicity of the mutations based on the mutant peptides’ strong binding with major histocompatibility complex class I molecules (MHC-I). The Kaplan-Meier method was used for the survival analysis. Results We observed that the chromatin modification pathway was significantly mutated across all clinical stages. Among the mutated genes involved in this pathway, we observed that the histone modification regulators were primarily mutated. Interestingly, of the 197 mutations in the 26 epigenetic regulators in this pathway, 25 missense mutations in 13 genes were predicted in or around the phosphorylation sites. Only mutations in the histone methyltransferase MLL2 exhibited poor survival. Compared to other mutations in MLL2 mutant patients, we noticed that the mutational scores prioritized mutations in MLL2, which indicates that it is more likely to have deleterious effects to the human genome. Around half of all of the mutations were found to bind strongly to MHC-I, suggesting that patients are likely to benefit from immunotherapy. Conclusions Our results highlight the emerging role of mutations in epigenetic regulators, particularly MLL2, in cervical carcinogenesis, which suggests a potential disruption of histone modifications. These data have implications for further investigation of the mechanism of epigenetic dysregulation and for treatment of cervical cancer. © The Author(s). 2017 |
abstractGer |
Background Cervical cancer is the second most common cause of cancer deaths in women worldwide. The aim of this study is to exploit novel pathogenic genes in cervical carcinogenesis. Method The somatic mutations from 194 patients with cervical cancer were obtained from the Cancer Genome Atlas (TCGA) publically accessible exome-sequencing database. We investigated mutated gene enrichment in the 12 cancer core pathways and predicted possible post-translational modifications. Additionally, we predicted the impact of mutations by scores quantifying the deleterious effects of the mutations. We also examined the immunogenicity of the mutations based on the mutant peptides’ strong binding with major histocompatibility complex class I molecules (MHC-I). The Kaplan-Meier method was used for the survival analysis. Results We observed that the chromatin modification pathway was significantly mutated across all clinical stages. Among the mutated genes involved in this pathway, we observed that the histone modification regulators were primarily mutated. Interestingly, of the 197 mutations in the 26 epigenetic regulators in this pathway, 25 missense mutations in 13 genes were predicted in or around the phosphorylation sites. Only mutations in the histone methyltransferase MLL2 exhibited poor survival. Compared to other mutations in MLL2 mutant patients, we noticed that the mutational scores prioritized mutations in MLL2, which indicates that it is more likely to have deleterious effects to the human genome. Around half of all of the mutations were found to bind strongly to MHC-I, suggesting that patients are likely to benefit from immunotherapy. Conclusions Our results highlight the emerging role of mutations in epigenetic regulators, particularly MLL2, in cervical carcinogenesis, which suggests a potential disruption of histone modifications. These data have implications for further investigation of the mechanism of epigenetic dysregulation and for treatment of cervical cancer. © The Author(s). 2017 |
abstract_unstemmed |
Background Cervical cancer is the second most common cause of cancer deaths in women worldwide. The aim of this study is to exploit novel pathogenic genes in cervical carcinogenesis. Method The somatic mutations from 194 patients with cervical cancer were obtained from the Cancer Genome Atlas (TCGA) publically accessible exome-sequencing database. We investigated mutated gene enrichment in the 12 cancer core pathways and predicted possible post-translational modifications. Additionally, we predicted the impact of mutations by scores quantifying the deleterious effects of the mutations. We also examined the immunogenicity of the mutations based on the mutant peptides’ strong binding with major histocompatibility complex class I molecules (MHC-I). The Kaplan-Meier method was used for the survival analysis. Results We observed that the chromatin modification pathway was significantly mutated across all clinical stages. Among the mutated genes involved in this pathway, we observed that the histone modification regulators were primarily mutated. Interestingly, of the 197 mutations in the 26 epigenetic regulators in this pathway, 25 missense mutations in 13 genes were predicted in or around the phosphorylation sites. Only mutations in the histone methyltransferase MLL2 exhibited poor survival. Compared to other mutations in MLL2 mutant patients, we noticed that the mutational scores prioritized mutations in MLL2, which indicates that it is more likely to have deleterious effects to the human genome. Around half of all of the mutations were found to bind strongly to MHC-I, suggesting that patients are likely to benefit from immunotherapy. Conclusions Our results highlight the emerging role of mutations in epigenetic regulators, particularly MLL2, in cervical carcinogenesis, which suggests a potential disruption of histone modifications. These data have implications for further investigation of the mechanism of epigenetic dysregulation and for treatment of cervical cancer. © The Author(s). 2017 |
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Emerging role of mutations in epigenetic regulators including MLL2 derived from The Cancer Genome Atlas for cervical cancer |
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