Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer

Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether D...
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Autor*in:	Isaac E. Kim [verfasserIn] Sinae Kim [verfasserIn] Arnav Srivastava [verfasserIn] Biren Saraiya [verfasserIn] Tina Mayer [verfasserIn] Wun-Jae Kim [verfasserIn] Isaac Yi Kim [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Übergeordnetes Werk:	In: BMC Urology - BMC, 2003, 19(2019), 1, Seite 6
Übergeordnetes Werk:	volume:19 ; year:2019 ; number:1 ; pages:6

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12894-019-0453-9

Katalog-ID:	DOAJ019444540

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520			\|a Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. Methods TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. Results DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA < 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). Conclusions Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease.
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allfields	10.1186/s12894-019-0453-9 doi (DE-627)DOAJ019444540 (DE-599)DOAJf5423f2580b04aa2b8f3842b255f6373 DE-627 ger DE-627 rakwb eng RC870-923 Isaac E. Kim verfasserin aut Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. Methods TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. Results DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA < 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). Conclusions Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease. Diseases of the genitourinary system. Urology Sinae Kim verfasserin aut Arnav Srivastava verfasserin aut Biren Saraiya verfasserin aut Tina Mayer verfasserin aut Wun-Jae Kim verfasserin aut Isaac Yi Kim verfasserin aut In BMC Urology BMC, 2003 19(2019), 1, Seite 6 (DE-627)335488811 (DE-600)2059857-9 14712490 nnns volume:19 year:2019 number:1 pages:6 https://doi.org/10.1186/s12894-019-0453-9 kostenfrei https://doaj.org/article/f5423f2580b04aa2b8f3842b255f6373 kostenfrei http://link.springer.com/article/10.1186/s12894-019-0453-9 kostenfrei https://doaj.org/toc/1471-2490 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 19 2019 1 6
spelling	10.1186/s12894-019-0453-9 doi (DE-627)DOAJ019444540 (DE-599)DOAJf5423f2580b04aa2b8f3842b255f6373 DE-627 ger DE-627 rakwb eng RC870-923 Isaac E. Kim verfasserin aut Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. Methods TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. Results DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA < 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). Conclusions Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease. Diseases of the genitourinary system. Urology Sinae Kim verfasserin aut Arnav Srivastava verfasserin aut Biren Saraiya verfasserin aut Tina Mayer verfasserin aut Wun-Jae Kim verfasserin aut Isaac Yi Kim verfasserin aut In BMC Urology BMC, 2003 19(2019), 1, Seite 6 (DE-627)335488811 (DE-600)2059857-9 14712490 nnns volume:19 year:2019 number:1 pages:6 https://doi.org/10.1186/s12894-019-0453-9 kostenfrei https://doaj.org/article/f5423f2580b04aa2b8f3842b255f6373 kostenfrei http://link.springer.com/article/10.1186/s12894-019-0453-9 kostenfrei https://doaj.org/toc/1471-2490 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 19 2019 1 6
allfields_unstemmed	10.1186/s12894-019-0453-9 doi (DE-627)DOAJ019444540 (DE-599)DOAJf5423f2580b04aa2b8f3842b255f6373 DE-627 ger DE-627 rakwb eng RC870-923 Isaac E. Kim verfasserin aut Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. Methods TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. Results DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA < 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). Conclusions Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease. Diseases of the genitourinary system. Urology Sinae Kim verfasserin aut Arnav Srivastava verfasserin aut Biren Saraiya verfasserin aut Tina Mayer verfasserin aut Wun-Jae Kim verfasserin aut Isaac Yi Kim verfasserin aut In BMC Urology BMC, 2003 19(2019), 1, Seite 6 (DE-627)335488811 (DE-600)2059857-9 14712490 nnns volume:19 year:2019 number:1 pages:6 https://doi.org/10.1186/s12894-019-0453-9 kostenfrei https://doaj.org/article/f5423f2580b04aa2b8f3842b255f6373 kostenfrei http://link.springer.com/article/10.1186/s12894-019-0453-9 kostenfrei https://doaj.org/toc/1471-2490 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 19 2019 1 6
allfieldsGer	10.1186/s12894-019-0453-9 doi (DE-627)DOAJ019444540 (DE-599)DOAJf5423f2580b04aa2b8f3842b255f6373 DE-627 ger DE-627 rakwb eng RC870-923 Isaac E. Kim verfasserin aut Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. Methods TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. Results DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA < 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). Conclusions Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease. Diseases of the genitourinary system. Urology Sinae Kim verfasserin aut Arnav Srivastava verfasserin aut Biren Saraiya verfasserin aut Tina Mayer verfasserin aut Wun-Jae Kim verfasserin aut Isaac Yi Kim verfasserin aut In BMC Urology BMC, 2003 19(2019), 1, Seite 6 (DE-627)335488811 (DE-600)2059857-9 14712490 nnns volume:19 year:2019 number:1 pages:6 https://doi.org/10.1186/s12894-019-0453-9 kostenfrei https://doaj.org/article/f5423f2580b04aa2b8f3842b255f6373 kostenfrei http://link.springer.com/article/10.1186/s12894-019-0453-9 kostenfrei https://doaj.org/toc/1471-2490 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 19 2019 1 6
allfieldsSound	10.1186/s12894-019-0453-9 doi (DE-627)DOAJ019444540 (DE-599)DOAJf5423f2580b04aa2b8f3842b255f6373 DE-627 ger DE-627 rakwb eng RC870-923 Isaac E. Kim verfasserin aut Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. Methods TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. Results DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA < 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). Conclusions Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease. Diseases of the genitourinary system. Urology Sinae Kim verfasserin aut Arnav Srivastava verfasserin aut Biren Saraiya verfasserin aut Tina Mayer verfasserin aut Wun-Jae Kim verfasserin aut Isaac Yi Kim verfasserin aut In BMC Urology BMC, 2003 19(2019), 1, Seite 6 (DE-627)335488811 (DE-600)2059857-9 14712490 nnns volume:19 year:2019 number:1 pages:6 https://doi.org/10.1186/s12894-019-0453-9 kostenfrei https://doaj.org/article/f5423f2580b04aa2b8f3842b255f6373 kostenfrei http://link.springer.com/article/10.1186/s12894-019-0453-9 kostenfrei https://doaj.org/toc/1471-2490 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 19 2019 1 6
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Kim</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. Methods TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. Results DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA < 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). 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callnumber-first	R - Medicine
author	Isaac E. Kim
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topic_title	RC870-923 Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer
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title	Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer
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title_full	Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer
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author_browse	Isaac E. Kim Sinae Kim Arnav Srivastava Biren Saraiya Tina Mayer Wun-Jae Kim Isaac Yi Kim
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title_sort	similar incidence of dna damage response pathway alterations between clinically localized and metastatic prostate cancer
callnumber	RC870-923
title_auth	Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer
abstract	Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. Methods TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. Results DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA < 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). Conclusions Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease.
abstractGer	Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. Methods TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. Results DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA < 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). Conclusions Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease.
abstract_unstemmed	Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. Methods TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. Results DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA < 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). Conclusions Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease.
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title_short	Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer
url	https://doi.org/10.1186/s12894-019-0453-9 https://doaj.org/article/f5423f2580b04aa2b8f3842b255f6373 http://link.springer.com/article/10.1186/s12894-019-0453-9 https://doaj.org/toc/1471-2490
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Kim</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. 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