BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer
The significant activity of poly(ADP-ribose)polymerase (PARP) inhibitors in the treatment of germline BRCA mutation-associated ovarian cancer, which represents ∼15% of HGS cases, has recently led to European Medicines Agency and food and drug administration approval of olaparib. Accumulating evidenc...
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| Veröffentlicht in: | Annals of oncology 2016-08, Vol.27 (8), p.1449-1455 |
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| creator | Moschetta, M. George, A. Kaye, S.B. Banerjee, S. |
| description | The significant activity of poly(ADP-ribose)polymerase (PARP) inhibitors in the treatment of germline BRCA mutation-associated ovarian cancer, which represents ∼15% of HGS cases, has recently led to European Medicines Agency and food and drug administration approval of olaparib. Accumulating evidence suggests that PARP inhibitors may have a wider application in the treatment of sporadic ovarian cancers. Up to 50% of HGS ovarian cancer patients may exhibit homologous recombination deficiency (HRD) through mechanisms including germline BRCA mutations, somatic BRCA mutations, and BRCA promoter methylation. In this review, we discuss the role of somatic BRCA mutations and BRCA methylation in ovarian cancer. There is accumulating evidence for routine somatic BRCA mutation testing, but the relevance of BRCA epigenetic modifications is less clear. We explore the challenges that need to be addressed if the full potential of these markers of HRD is to be utilised in clinical practice. |
| doi_str_mv | 10.1093/annonc/mdw142 |
| format | Article |
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Accumulating evidence suggests that PARP inhibitors may have a wider application in the treatment of sporadic ovarian cancers. Up to 50% of HGS ovarian cancer patients may exhibit homologous recombination deficiency (HRD) through mechanisms including germline BRCA mutations, somatic BRCA mutations, and BRCA promoter methylation. In this review, we discuss the role of somatic BRCA mutations and BRCA methylation in ovarian cancer. There is accumulating evidence for routine somatic BRCA mutation testing, but the relevance of BRCA epigenetic modifications is less clear. We explore the challenges that need to be addressed if the full potential of these markers of HRD is to be utilised in clinical practice.</description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1093/annonc/mdw142</identifier><identifier>PMID: 27037296</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>BRCA ; BRCA1 Protein - genetics ; BRCA2 Protein - genetics ; Cystadenocarcinoma, Serous - drug therapy ; Cystadenocarcinoma, Serous - genetics ; Cystadenocarcinoma, Serous - pathology ; DNA Methylation - drug effects ; Female ; Germ-Line Mutation - genetics ; Homologous Recombination - drug effects ; Humans ; methylation ; ovarian cancer ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - pathology ; Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use ; somatic mutation</subject><ispartof>Annals of oncology, 2016-08, Vol.27 (8), p.1449-1455</ispartof><rights>2016 European Society for Medical Oncology</rights><rights>The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. 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Accumulating evidence suggests that PARP inhibitors may have a wider application in the treatment of sporadic ovarian cancers. Up to 50% of HGS ovarian cancer patients may exhibit homologous recombination deficiency (HRD) through mechanisms including germline BRCA mutations, somatic BRCA mutations, and BRCA promoter methylation. In this review, we discuss the role of somatic BRCA mutations and BRCA methylation in ovarian cancer. There is accumulating evidence for routine somatic BRCA mutation testing, but the relevance of BRCA epigenetic modifications is less clear. We explore the challenges that need to be addressed if the full potential of these markers of HRD is to be utilised in clinical practice.</description><subject>BRCA</subject><subject>BRCA1 Protein - genetics</subject><subject>BRCA2 Protein - genetics</subject><subject>Cystadenocarcinoma, Serous - drug therapy</subject><subject>Cystadenocarcinoma, Serous - genetics</subject><subject>Cystadenocarcinoma, Serous - pathology</subject><subject>DNA Methylation - drug effects</subject><subject>Female</subject><subject>Germ-Line Mutation - genetics</subject><subject>Homologous Recombination - drug effects</subject><subject>Humans</subject><subject>methylation</subject><subject>ovarian cancer</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use</subject><subject>somatic mutation</subject><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kDtPwzAUhS0EoqUwsqKMLKF-JbbHUvGSKiEQzJZj3yKjxi52WsS_JyWFjekM99PRPR9C5wRfEazY1IQQg5227pNweoDGpKpVKTEnh2iMFWWlqBgfoZOc3zHGtaLqGI2owExQVY_R0_XzfFbk2JrO26LddH3GkAsTXAFr_wYBdocfqo3OL73dEz4UGVLc5CJuTfImFNYEC-kUHS3NKsPZPifo9fbmZX5fLh7vHuazRWk5r7uSYbJUUElpa4lpRQSnwjVWUqkqaBrCBbPC1I00vAJeY9rghjU1FwZb45xlE3Q59K5T_NhA7nTrs4XVygTov9JEYkGFUkz2aDmgNsWcEyz1OvnWpC9NsN5Z1INFPVjs-Yt99aZpwf3Rv9p6QAwA9AO3HpLO1kO_3vkEttMu-n-qvwFOW4Mz</recordid><startdate>201608</startdate><enddate>201608</enddate><creator>Moschetta, M.</creator><creator>George, A.</creator><creator>Kaye, S.B.</creator><creator>Banerjee, S.</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201608</creationdate><title>BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer</title><author>Moschetta, M. ; George, A. ; Kaye, S.B. ; Banerjee, S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-301f9e588c6802517427dbc82895ebb1473c7a6b8a45e4602b0b3b647a0caddc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>BRCA</topic><topic>BRCA1 Protein - genetics</topic><topic>BRCA2 Protein - genetics</topic><topic>Cystadenocarcinoma, Serous - drug therapy</topic><topic>Cystadenocarcinoma, Serous - genetics</topic><topic>Cystadenocarcinoma, Serous - pathology</topic><topic>DNA Methylation - drug effects</topic><topic>Female</topic><topic>Germ-Line Mutation - genetics</topic><topic>Homologous Recombination - drug effects</topic><topic>Humans</topic><topic>methylation</topic><topic>ovarian cancer</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use</topic><topic>somatic mutation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moschetta, M.</creatorcontrib><creatorcontrib>George, A.</creatorcontrib><creatorcontrib>Kaye, S.B.</creatorcontrib><creatorcontrib>Banerjee, S.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moschetta, M.</au><au>George, A.</au><au>Kaye, S.B.</au><au>Banerjee, S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer</atitle><jtitle>Annals of oncology</jtitle><addtitle>Ann Oncol</addtitle><date>2016-08</date><risdate>2016</risdate><volume>27</volume><issue>8</issue><spage>1449</spage><epage>1455</epage><pages>1449-1455</pages><issn>0923-7534</issn><eissn>1569-8041</eissn><abstract>The significant activity of poly(ADP-ribose)polymerase (PARP) inhibitors in the treatment of germline BRCA mutation-associated ovarian cancer, which represents ∼15% of HGS cases, has recently led to European Medicines Agency and food and drug administration approval of olaparib. 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| issn | 0923-7534 1569-8041 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | BRCA BRCA1 Protein - genetics BRCA2 Protein - genetics Cystadenocarcinoma, Serous - drug therapy Cystadenocarcinoma, Serous - genetics Cystadenocarcinoma, Serous - pathology DNA Methylation - drug effects Female Germ-Line Mutation - genetics Homologous Recombination - drug effects Humans methylation ovarian cancer Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use somatic mutation |
| title | BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer |
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