Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response

Objective: We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients treated with olaparib to investigate the relationship between intratumor heterogeneity and response to olaparib treatment. The main aim is to identify possible predictive biomarkers of respons...
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Gespeichert in:

Autor*in:	Elisena Franzese [verfasserIn] Sara Centonze [verfasserIn] Anna Diana [verfasserIn] Angela Lombardi [verfasserIn] Francesca Carlino [verfasserIn] Luigi Pio Guerrera [verfasserIn] Ferdinando De Vita [verfasserIn] Michele Caraglia [verfasserIn] Sandro Pignata [verfasserIn] Fortunato Ciardiello [verfasserIn] Michele Orditura [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	ovarian cancer genomic profiles BRCA 1/2 mutation carriers promoter methylation olaparib (Lynparza™)

Übergeordnetes Werk:	In: Frontiers in Oncology - Frontiers Media S.A., 2012, 9(2019)
Übergeordnetes Werk:	volume:9 ; year:2019

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fonc.2019.01289

Katalog-ID:	DOAJ041128745

Internformat


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245	1	0	\|a Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response
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520			\|a Objective: We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients treated with olaparib to investigate the relationship between intratumor heterogeneity and response to olaparib treatment. The main aim is to identify possible predictive biomarkers of response to olaparib through the analysis of HRD or not HRD genes and the definition of BRCA1 promoter methylation status.Methods: DNA, isolated from formalin-fixed, paraffin-embedded (FFPE) diagnostic OC tissues, was analyzed by FoundationOneCDx™. This assay detects alterations in a total panel of 324 genes, using the Illumina® HiSeq 4000 platform. Methylation analysis of the BRCA gene promoter was carried out by pyrosequencing with PyroMark Q24 platform (Qiagen), an in vitro nucleic acid sequence-based detection test based on pyrosequencing technology for quantitative measurements of methylation status.Results: Case #1 and #2 were defined Long-term responders since they received olaparib for 27 and 36 months, respectively. These remarkable results could be explained, at least in part, by the presence of somatic IDH1 mutation in case #1 and PI3K and SOX2 amplification in the case #2. In case #3, the somatic NF1 mutation appeared to be related to the short duration of response. In the case #4, in which the patients is on olaparib from 1 year achieving a stable disease, a somatic mutation of BRCA1 was recorded. Moreover, in all cases, levels of BRCA1 promoter were strictly related to olaparib response.Conclusions: Based on our experience, genomic analysis of tumor tissue at diagnosis might help to determine the future response to olaparib in advanced OC setting, revealing predictive biomarkers beyond BRCA 1-2 and HRD status.
650		4	\|a ovarian cancer
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650		4	\|a BRCA 1/2 mutation carriers
650		4	\|a promoter methylation
650		4	\|a olaparib (Lynparza™)
653		0	\|a Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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700	0		\|a Michele Orditura \|e verfasserin \|4 aut
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author_variant	e f ef s c sc a d ad a l al f c fc l p g lpg f d v fdv m c mc s p sp f c fc m o mo
matchkey_str	article:2234943X:2019----::eoipoienbc1rmtrehltosauibcmttdvracnenwnihsnrdc
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allfields	10.3389/fonc.2019.01289 doi (DE-627)DOAJ041128745 (DE-599)DOAJa4cb591f5ba34c5987d5dc70f6b04451 DE-627 ger DE-627 rakwb eng RC254-282 Elisena Franzese verfasserin aut Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients treated with olaparib to investigate the relationship between intratumor heterogeneity and response to olaparib treatment. The main aim is to identify possible predictive biomarkers of response to olaparib through the analysis of HRD or not HRD genes and the definition of BRCA1 promoter methylation status.Methods: DNA, isolated from formalin-fixed, paraffin-embedded (FFPE) diagnostic OC tissues, was analyzed by FoundationOneCDx™. This assay detects alterations in a total panel of 324 genes, using the Illumina® HiSeq 4000 platform. Methylation analysis of the BRCA gene promoter was carried out by pyrosequencing with PyroMark Q24 platform (Qiagen), an in vitro nucleic acid sequence-based detection test based on pyrosequencing technology for quantitative measurements of methylation status.Results: Case #1 and #2 were defined Long-term responders since they received olaparib for 27 and 36 months, respectively. These remarkable results could be explained, at least in part, by the presence of somatic IDH1 mutation in case #1 and PI3K and SOX2 amplification in the case #2. In case #3, the somatic NF1 mutation appeared to be related to the short duration of response. In the case #4, in which the patients is on olaparib from 1 year achieving a stable disease, a somatic mutation of BRCA1 was recorded. Moreover, in all cases, levels of BRCA1 promoter were strictly related to olaparib response.Conclusions: Based on our experience, genomic analysis of tumor tissue at diagnosis might help to determine the future response to olaparib in advanced OC setting, revealing predictive biomarkers beyond BRCA 1-2 and HRD status. ovarian cancer genomic profiles BRCA 1/2 mutation carriers promoter methylation olaparib (Lynparza™) Neoplasms. Tumors. Oncology. Including cancer and carcinogens Sara Centonze verfasserin aut Anna Diana verfasserin aut Angela Lombardi verfasserin aut Francesca Carlino verfasserin aut Luigi Pio Guerrera verfasserin aut Ferdinando De Vita verfasserin aut Michele Caraglia verfasserin aut Sandro Pignata verfasserin aut Fortunato Ciardiello verfasserin aut Michele Orditura verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 9(2019) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:9 year:2019 https://doi.org/10.3389/fonc.2019.01289 kostenfrei https://doaj.org/article/a4cb591f5ba34c5987d5dc70f6b04451 kostenfrei https://www.frontiersin.org/article/10.3389/fonc.2019.01289/full kostenfrei https://doaj.org/toc/2234-943X 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_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_2003 GBV_ILN_2014 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 9 2019
spelling	10.3389/fonc.2019.01289 doi (DE-627)DOAJ041128745 (DE-599)DOAJa4cb591f5ba34c5987d5dc70f6b04451 DE-627 ger DE-627 rakwb eng RC254-282 Elisena Franzese verfasserin aut Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients treated with olaparib to investigate the relationship between intratumor heterogeneity and response to olaparib treatment. The main aim is to identify possible predictive biomarkers of response to olaparib through the analysis of HRD or not HRD genes and the definition of BRCA1 promoter methylation status.Methods: DNA, isolated from formalin-fixed, paraffin-embedded (FFPE) diagnostic OC tissues, was analyzed by FoundationOneCDx™. This assay detects alterations in a total panel of 324 genes, using the Illumina® HiSeq 4000 platform. Methylation analysis of the BRCA gene promoter was carried out by pyrosequencing with PyroMark Q24 platform (Qiagen), an in vitro nucleic acid sequence-based detection test based on pyrosequencing technology for quantitative measurements of methylation status.Results: Case #1 and #2 were defined Long-term responders since they received olaparib for 27 and 36 months, respectively. These remarkable results could be explained, at least in part, by the presence of somatic IDH1 mutation in case #1 and PI3K and SOX2 amplification in the case #2. In case #3, the somatic NF1 mutation appeared to be related to the short duration of response. In the case #4, in which the patients is on olaparib from 1 year achieving a stable disease, a somatic mutation of BRCA1 was recorded. Moreover, in all cases, levels of BRCA1 promoter were strictly related to olaparib response.Conclusions: Based on our experience, genomic analysis of tumor tissue at diagnosis might help to determine the future response to olaparib in advanced OC setting, revealing predictive biomarkers beyond BRCA 1-2 and HRD status. ovarian cancer genomic profiles BRCA 1/2 mutation carriers promoter methylation olaparib (Lynparza™) Neoplasms. Tumors. Oncology. Including cancer and carcinogens Sara Centonze verfasserin aut Anna Diana verfasserin aut Angela Lombardi verfasserin aut Francesca Carlino verfasserin aut Luigi Pio Guerrera verfasserin aut Ferdinando De Vita verfasserin aut Michele Caraglia verfasserin aut Sandro Pignata verfasserin aut Fortunato Ciardiello verfasserin aut Michele Orditura verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 9(2019) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:9 year:2019 https://doi.org/10.3389/fonc.2019.01289 kostenfrei https://doaj.org/article/a4cb591f5ba34c5987d5dc70f6b04451 kostenfrei https://www.frontiersin.org/article/10.3389/fonc.2019.01289/full kostenfrei https://doaj.org/toc/2234-943X 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_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_2003 GBV_ILN_2014 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 9 2019
allfields_unstemmed	10.3389/fonc.2019.01289 doi (DE-627)DOAJ041128745 (DE-599)DOAJa4cb591f5ba34c5987d5dc70f6b04451 DE-627 ger DE-627 rakwb eng RC254-282 Elisena Franzese verfasserin aut Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients treated with olaparib to investigate the relationship between intratumor heterogeneity and response to olaparib treatment. The main aim is to identify possible predictive biomarkers of response to olaparib through the analysis of HRD or not HRD genes and the definition of BRCA1 promoter methylation status.Methods: DNA, isolated from formalin-fixed, paraffin-embedded (FFPE) diagnostic OC tissues, was analyzed by FoundationOneCDx™. This assay detects alterations in a total panel of 324 genes, using the Illumina® HiSeq 4000 platform. Methylation analysis of the BRCA gene promoter was carried out by pyrosequencing with PyroMark Q24 platform (Qiagen), an in vitro nucleic acid sequence-based detection test based on pyrosequencing technology for quantitative measurements of methylation status.Results: Case #1 and #2 were defined Long-term responders since they received olaparib for 27 and 36 months, respectively. These remarkable results could be explained, at least in part, by the presence of somatic IDH1 mutation in case #1 and PI3K and SOX2 amplification in the case #2. In case #3, the somatic NF1 mutation appeared to be related to the short duration of response. In the case #4, in which the patients is on olaparib from 1 year achieving a stable disease, a somatic mutation of BRCA1 was recorded. Moreover, in all cases, levels of BRCA1 promoter were strictly related to olaparib response.Conclusions: Based on our experience, genomic analysis of tumor tissue at diagnosis might help to determine the future response to olaparib in advanced OC setting, revealing predictive biomarkers beyond BRCA 1-2 and HRD status. ovarian cancer genomic profiles BRCA 1/2 mutation carriers promoter methylation olaparib (Lynparza™) Neoplasms. Tumors. Oncology. Including cancer and carcinogens Sara Centonze verfasserin aut Anna Diana verfasserin aut Angela Lombardi verfasserin aut Francesca Carlino verfasserin aut Luigi Pio Guerrera verfasserin aut Ferdinando De Vita verfasserin aut Michele Caraglia verfasserin aut Sandro Pignata verfasserin aut Fortunato Ciardiello verfasserin aut Michele Orditura verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 9(2019) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:9 year:2019 https://doi.org/10.3389/fonc.2019.01289 kostenfrei https://doaj.org/article/a4cb591f5ba34c5987d5dc70f6b04451 kostenfrei https://www.frontiersin.org/article/10.3389/fonc.2019.01289/full kostenfrei https://doaj.org/toc/2234-943X 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_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_2003 GBV_ILN_2014 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 9 2019
allfieldsGer	10.3389/fonc.2019.01289 doi (DE-627)DOAJ041128745 (DE-599)DOAJa4cb591f5ba34c5987d5dc70f6b04451 DE-627 ger DE-627 rakwb eng RC254-282 Elisena Franzese verfasserin aut Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients treated with olaparib to investigate the relationship between intratumor heterogeneity and response to olaparib treatment. The main aim is to identify possible predictive biomarkers of response to olaparib through the analysis of HRD or not HRD genes and the definition of BRCA1 promoter methylation status.Methods: DNA, isolated from formalin-fixed, paraffin-embedded (FFPE) diagnostic OC tissues, was analyzed by FoundationOneCDx™. This assay detects alterations in a total panel of 324 genes, using the Illumina® HiSeq 4000 platform. Methylation analysis of the BRCA gene promoter was carried out by pyrosequencing with PyroMark Q24 platform (Qiagen), an in vitro nucleic acid sequence-based detection test based on pyrosequencing technology for quantitative measurements of methylation status.Results: Case #1 and #2 were defined Long-term responders since they received olaparib for 27 and 36 months, respectively. These remarkable results could be explained, at least in part, by the presence of somatic IDH1 mutation in case #1 and PI3K and SOX2 amplification in the case #2. In case #3, the somatic NF1 mutation appeared to be related to the short duration of response. In the case #4, in which the patients is on olaparib from 1 year achieving a stable disease, a somatic mutation of BRCA1 was recorded. Moreover, in all cases, levels of BRCA1 promoter were strictly related to olaparib response.Conclusions: Based on our experience, genomic analysis of tumor tissue at diagnosis might help to determine the future response to olaparib in advanced OC setting, revealing predictive biomarkers beyond BRCA 1-2 and HRD status. ovarian cancer genomic profiles BRCA 1/2 mutation carriers promoter methylation olaparib (Lynparza™) Neoplasms. Tumors. Oncology. Including cancer and carcinogens Sara Centonze verfasserin aut Anna Diana verfasserin aut Angela Lombardi verfasserin aut Francesca Carlino verfasserin aut Luigi Pio Guerrera verfasserin aut Ferdinando De Vita verfasserin aut Michele Caraglia verfasserin aut Sandro Pignata verfasserin aut Fortunato Ciardiello verfasserin aut Michele Orditura verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 9(2019) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:9 year:2019 https://doi.org/10.3389/fonc.2019.01289 kostenfrei https://doaj.org/article/a4cb591f5ba34c5987d5dc70f6b04451 kostenfrei https://www.frontiersin.org/article/10.3389/fonc.2019.01289/full kostenfrei https://doaj.org/toc/2234-943X 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_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_2003 GBV_ILN_2014 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 9 2019
allfieldsSound	10.3389/fonc.2019.01289 doi (DE-627)DOAJ041128745 (DE-599)DOAJa4cb591f5ba34c5987d5dc70f6b04451 DE-627 ger DE-627 rakwb eng RC254-282 Elisena Franzese verfasserin aut Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients treated with olaparib to investigate the relationship between intratumor heterogeneity and response to olaparib treatment. The main aim is to identify possible predictive biomarkers of response to olaparib through the analysis of HRD or not HRD genes and the definition of BRCA1 promoter methylation status.Methods: DNA, isolated from formalin-fixed, paraffin-embedded (FFPE) diagnostic OC tissues, was analyzed by FoundationOneCDx™. This assay detects alterations in a total panel of 324 genes, using the Illumina® HiSeq 4000 platform. Methylation analysis of the BRCA gene promoter was carried out by pyrosequencing with PyroMark Q24 platform (Qiagen), an in vitro nucleic acid sequence-based detection test based on pyrosequencing technology for quantitative measurements of methylation status.Results: Case #1 and #2 were defined Long-term responders since they received olaparib for 27 and 36 months, respectively. These remarkable results could be explained, at least in part, by the presence of somatic IDH1 mutation in case #1 and PI3K and SOX2 amplification in the case #2. In case #3, the somatic NF1 mutation appeared to be related to the short duration of response. In the case #4, in which the patients is on olaparib from 1 year achieving a stable disease, a somatic mutation of BRCA1 was recorded. Moreover, in all cases, levels of BRCA1 promoter were strictly related to olaparib response.Conclusions: Based on our experience, genomic analysis of tumor tissue at diagnosis might help to determine the future response to olaparib in advanced OC setting, revealing predictive biomarkers beyond BRCA 1-2 and HRD status. ovarian cancer genomic profiles BRCA 1/2 mutation carriers promoter methylation olaparib (Lynparza™) Neoplasms. Tumors. Oncology. Including cancer and carcinogens Sara Centonze verfasserin aut Anna Diana verfasserin aut Angela Lombardi verfasserin aut Francesca Carlino verfasserin aut Luigi Pio Guerrera verfasserin aut Ferdinando De Vita verfasserin aut Michele Caraglia verfasserin aut Sandro Pignata verfasserin aut Fortunato Ciardiello verfasserin aut Michele Orditura verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 9(2019) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:9 year:2019 https://doi.org/10.3389/fonc.2019.01289 kostenfrei https://doaj.org/article/a4cb591f5ba34c5987d5dc70f6b04451 kostenfrei https://www.frontiersin.org/article/10.3389/fonc.2019.01289/full kostenfrei https://doaj.org/toc/2234-943X 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_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_2003 GBV_ILN_2014 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 9 2019
language	English
source	In Frontiers in Oncology 9(2019) volume:9 year:2019
sourceStr	In Frontiers in Oncology 9(2019) volume:9 year:2019
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	ovarian cancer genomic profiles BRCA 1/2 mutation carriers promoter methylation olaparib (Lynparza™) Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Frontiers in Oncology
authorswithroles_txt_mv	Elisena Franzese @@aut@@ Sara Centonze @@aut@@ Anna Diana @@aut@@ Angela Lombardi @@aut@@ Francesca Carlino @@aut@@ Luigi Pio Guerrera @@aut@@ Ferdinando De Vita @@aut@@ Michele Caraglia @@aut@@ Sandro Pignata @@aut@@ Fortunato Ciardiello @@aut@@ Michele Orditura @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
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topic_title	RC254-282 Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response ovarian cancer genomic profiles BRCA 1/2 mutation carriers promoter methylation olaparib (Lynparza™)
topic	misc RC254-282 misc ovarian cancer misc genomic profiles misc BRCA 1/2 mutation carriers misc promoter methylation misc olaparib (Lynparza™) misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc ovarian cancer misc genomic profiles misc BRCA 1/2 mutation carriers misc promoter methylation misc olaparib (Lynparza™) misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc ovarian cancer misc genomic profiles misc BRCA 1/2 mutation carriers misc promoter methylation misc olaparib (Lynparza™) misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response
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title_full	Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response
author_sort	Elisena Franzese
journal	Frontiers in Oncology
journalStr	Frontiers in Oncology
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author_browse	Elisena Franzese Sara Centonze Anna Diana Angela Lombardi Francesca Carlino Luigi Pio Guerrera Ferdinando De Vita Michele Caraglia Sandro Pignata Fortunato Ciardiello Michele Orditura
container_volume	9
class	RC254-282
format_se	Elektronische Aufsätze
author-letter	Elisena Franzese
doi_str_mv	10.3389/fonc.2019.01289
author2-role	verfasserin
title_sort	genomic profile and brca-1 promoter methylation status in brca mutated ovarian cancer: new insights in predictive biomarkers of olaparib response
callnumber	RC254-282
title_auth	Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response
abstract	Objective: We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients treated with olaparib to investigate the relationship between intratumor heterogeneity and response to olaparib treatment. The main aim is to identify possible predictive biomarkers of response to olaparib through the analysis of HRD or not HRD genes and the definition of BRCA1 promoter methylation status.Methods: DNA, isolated from formalin-fixed, paraffin-embedded (FFPE) diagnostic OC tissues, was analyzed by FoundationOneCDx™. This assay detects alterations in a total panel of 324 genes, using the Illumina® HiSeq 4000 platform. Methylation analysis of the BRCA gene promoter was carried out by pyrosequencing with PyroMark Q24 platform (Qiagen), an in vitro nucleic acid sequence-based detection test based on pyrosequencing technology for quantitative measurements of methylation status.Results: Case #1 and #2 were defined Long-term responders since they received olaparib for 27 and 36 months, respectively. These remarkable results could be explained, at least in part, by the presence of somatic IDH1 mutation in case #1 and PI3K and SOX2 amplification in the case #2. In case #3, the somatic NF1 mutation appeared to be related to the short duration of response. In the case #4, in which the patients is on olaparib from 1 year achieving a stable disease, a somatic mutation of BRCA1 was recorded. Moreover, in all cases, levels of BRCA1 promoter were strictly related to olaparib response.Conclusions: Based on our experience, genomic analysis of tumor tissue at diagnosis might help to determine the future response to olaparib in advanced OC setting, revealing predictive biomarkers beyond BRCA 1-2 and HRD status.
abstractGer	Objective: We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients treated with olaparib to investigate the relationship between intratumor heterogeneity and response to olaparib treatment. The main aim is to identify possible predictive biomarkers of response to olaparib through the analysis of HRD or not HRD genes and the definition of BRCA1 promoter methylation status.Methods: DNA, isolated from formalin-fixed, paraffin-embedded (FFPE) diagnostic OC tissues, was analyzed by FoundationOneCDx™. This assay detects alterations in a total panel of 324 genes, using the Illumina® HiSeq 4000 platform. Methylation analysis of the BRCA gene promoter was carried out by pyrosequencing with PyroMark Q24 platform (Qiagen), an in vitro nucleic acid sequence-based detection test based on pyrosequencing technology for quantitative measurements of methylation status.Results: Case #1 and #2 were defined Long-term responders since they received olaparib for 27 and 36 months, respectively. These remarkable results could be explained, at least in part, by the presence of somatic IDH1 mutation in case #1 and PI3K and SOX2 amplification in the case #2. In case #3, the somatic NF1 mutation appeared to be related to the short duration of response. In the case #4, in which the patients is on olaparib from 1 year achieving a stable disease, a somatic mutation of BRCA1 was recorded. Moreover, in all cases, levels of BRCA1 promoter were strictly related to olaparib response.Conclusions: Based on our experience, genomic analysis of tumor tissue at diagnosis might help to determine the future response to olaparib in advanced OC setting, revealing predictive biomarkers beyond BRCA 1-2 and HRD status.
abstract_unstemmed	Objective: We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients treated with olaparib to investigate the relationship between intratumor heterogeneity and response to olaparib treatment. The main aim is to identify possible predictive biomarkers of response to olaparib through the analysis of HRD or not HRD genes and the definition of BRCA1 promoter methylation status.Methods: DNA, isolated from formalin-fixed, paraffin-embedded (FFPE) diagnostic OC tissues, was analyzed by FoundationOneCDx™. This assay detects alterations in a total panel of 324 genes, using the Illumina® HiSeq 4000 platform. Methylation analysis of the BRCA gene promoter was carried out by pyrosequencing with PyroMark Q24 platform (Qiagen), an in vitro nucleic acid sequence-based detection test based on pyrosequencing technology for quantitative measurements of methylation status.Results: Case #1 and #2 were defined Long-term responders since they received olaparib for 27 and 36 months, respectively. These remarkable results could be explained, at least in part, by the presence of somatic IDH1 mutation in case #1 and PI3K and SOX2 amplification in the case #2. In case #3, the somatic NF1 mutation appeared to be related to the short duration of response. In the case #4, in which the patients is on olaparib from 1 year achieving a stable disease, a somatic mutation of BRCA1 was recorded. Moreover, in all cases, levels of BRCA1 promoter were strictly related to olaparib response.Conclusions: Based on our experience, genomic analysis of tumor tissue at diagnosis might help to determine the future response to olaparib in advanced OC setting, revealing predictive biomarkers beyond BRCA 1-2 and HRD status.
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title_short	Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response
url	https://doi.org/10.3389/fonc.2019.01289 https://doaj.org/article/a4cb591f5ba34c5987d5dc70f6b04451 https://www.frontiersin.org/article/10.3389/fonc.2019.01289/full https://doaj.org/toc/2234-943X
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author2	Sara Centonze Anna Diana Angela Lombardi Francesca Carlino Luigi Pio Guerrera Ferdinando De Vita Michele Caraglia Sandro Pignata Fortunato Ciardiello Michele Orditura
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up_date	2024-07-03T18:34:20.221Z
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