Variants on the promoter region of PTEN affect breast cancer progression and patient survival

Introduction The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Heikkinen, Tuomas [verfasserIn] Greco, Dario Pelttari, Liisa M Tommiska, Johanna Vahteristo, Pia Heikkilä, Päivi Blomqvist, Carl Aittomäki, Kristiina Nevanlinna, Heli

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2011

Schlagwörter:	Breast Cancer PTEN Expression PTEN Gene Distant Metastasis Free Survival Promoter Variant

Anmerkung:	© Heikkinen et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: Breast cancer research - London : BioMed Central, 1999, 13(2011), 6 vom: 15. Dez.
Übergeordnetes Werk:	volume:13 ; year:2011 ; number:6 ; day:15 ; month:12

Links:	Volltext

DOI / URN:	10.1186/bcr3076

Katalog-ID:	SPR029944953

Internformat


LEADER	01000caa a22002652 4500
001	SPR029944953
003	DE-627
005	20230519113832.0
007	cr uuu---uuuuu
008	201007s2011 xx \|\|\|\|\|o 00\| \|\|eng c
024	7		\|a 10.1186/bcr3076 \|2 doi
035			\|a (DE-627)SPR029944953
035			\|a (SPR)bcr3076-e
040			\|a DE-627 \|b ger \|c DE-627 \|e rakwb
041			\|a eng
100	1		\|a Heikkinen, Tuomas \|e verfasserin \|4 aut
245	1	0	\|a Variants on the promoter region of PTEN affect breast cancer progression and patient survival
264		1	\|c 2011
336			\|a Text \|b txt \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
500			\|a © Heikkinen et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (
520			\|a Introduction The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer. Methods We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes. Results All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets. Conclusions Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer.
650		4	\|a Breast Cancer \|7 (dpeaa)DE-He213
650		4	\|a PTEN Expression \|7 (dpeaa)DE-He213
650		4	\|a PTEN Gene \|7 (dpeaa)DE-He213
650		4	\|a Distant Metastasis Free Survival \|7 (dpeaa)DE-He213
650		4	\|a Promoter Variant \|7 (dpeaa)DE-He213
700	1		\|a Greco, Dario \|4 aut
700	1		\|a Pelttari, Liisa M \|4 aut
700	1		\|a Tommiska, Johanna \|4 aut
700	1		\|a Vahteristo, Pia \|4 aut
700	1		\|a Heikkilä, Päivi \|4 aut
700	1		\|a Blomqvist, Carl \|4 aut
700	1		\|a Aittomäki, Kristiina \|4 aut
700	1		\|a Nevanlinna, Heli \|4 aut
773	0	8	\|i Enthalten in \|t Breast cancer research \|d London : BioMed Central, 1999 \|g 13(2011), 6 vom: 15. Dez. \|w (DE-627)326645950 \|w (DE-600)2041618-0 \|x 1465-542X \|7 nnns
773	1	8	\|g volume:13 \|g year:2011 \|g number:6 \|g day:15 \|g month:12
856	4	0	\|u https://dx.doi.org/10.1186/bcr3076 \|z kostenfrei \|3 Volltext
912			\|a GBV_USEFLAG_A
912			\|a SYSFLAG_A
912			\|a GBV_SPRINGER
912			\|a SSG-OLC-PHA
912			\|a GBV_ILN_11
912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
912			\|a GBV_ILN_23
912			\|a GBV_ILN_24
912			\|a GBV_ILN_39
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_65
912			\|a GBV_ILN_69
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_95
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_151
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_206
912			\|a GBV_ILN_213
912			\|a GBV_ILN_230
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_602
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2106
912			\|a GBV_ILN_2232
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4700
951			\|a AR
952			\|d 13 \|j 2011 \|e 6 \|b 15 \|c 12

Indexfelder

author_variant	t h th d g dg l m p lm lmp j t jt p v pv p h ph c b cb k a ka h n hn
matchkey_str	article:1465542X:2011----::ainsnhpooergoopeafcbescneporsi
hierarchy_sort_str	2011
publishDate	2011
allfields	10.1186/bcr3076 doi (DE-627)SPR029944953 (SPR)bcr3076-e DE-627 ger DE-627 rakwb eng Heikkinen, Tuomas verfasserin aut Variants on the promoter region of PTEN affect breast cancer progression and patient survival 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Heikkinen et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( Introduction The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer. Methods We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes. Results All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets. Conclusions Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer. Breast Cancer (dpeaa)DE-He213 PTEN Expression (dpeaa)DE-He213 PTEN Gene (dpeaa)DE-He213 Distant Metastasis Free Survival (dpeaa)DE-He213 Promoter Variant (dpeaa)DE-He213 Greco, Dario aut Pelttari, Liisa M aut Tommiska, Johanna aut Vahteristo, Pia aut Heikkilä, Päivi aut Blomqvist, Carl aut Aittomäki, Kristiina aut Nevanlinna, Heli aut Enthalten in Breast cancer research London : BioMed Central, 1999 13(2011), 6 vom: 15. Dez. (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:13 year:2011 number:6 day:15 month:12 https://dx.doi.org/10.1186/bcr3076 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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_2005 GBV_ILN_2014 GBV_ILN_2106 GBV_ILN_2232 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 13 2011 6 15 12
spelling	10.1186/bcr3076 doi (DE-627)SPR029944953 (SPR)bcr3076-e DE-627 ger DE-627 rakwb eng Heikkinen, Tuomas verfasserin aut Variants on the promoter region of PTEN affect breast cancer progression and patient survival 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Heikkinen et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( Introduction The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer. Methods We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes. Results All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets. Conclusions Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer. Breast Cancer (dpeaa)DE-He213 PTEN Expression (dpeaa)DE-He213 PTEN Gene (dpeaa)DE-He213 Distant Metastasis Free Survival (dpeaa)DE-He213 Promoter Variant (dpeaa)DE-He213 Greco, Dario aut Pelttari, Liisa M aut Tommiska, Johanna aut Vahteristo, Pia aut Heikkilä, Päivi aut Blomqvist, Carl aut Aittomäki, Kristiina aut Nevanlinna, Heli aut Enthalten in Breast cancer research London : BioMed Central, 1999 13(2011), 6 vom: 15. Dez. (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:13 year:2011 number:6 day:15 month:12 https://dx.doi.org/10.1186/bcr3076 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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_2005 GBV_ILN_2014 GBV_ILN_2106 GBV_ILN_2232 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 13 2011 6 15 12
allfields_unstemmed	10.1186/bcr3076 doi (DE-627)SPR029944953 (SPR)bcr3076-e DE-627 ger DE-627 rakwb eng Heikkinen, Tuomas verfasserin aut Variants on the promoter region of PTEN affect breast cancer progression and patient survival 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Heikkinen et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( Introduction The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer. Methods We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes. Results All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets. Conclusions Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer. Breast Cancer (dpeaa)DE-He213 PTEN Expression (dpeaa)DE-He213 PTEN Gene (dpeaa)DE-He213 Distant Metastasis Free Survival (dpeaa)DE-He213 Promoter Variant (dpeaa)DE-He213 Greco, Dario aut Pelttari, Liisa M aut Tommiska, Johanna aut Vahteristo, Pia aut Heikkilä, Päivi aut Blomqvist, Carl aut Aittomäki, Kristiina aut Nevanlinna, Heli aut Enthalten in Breast cancer research London : BioMed Central, 1999 13(2011), 6 vom: 15. Dez. (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:13 year:2011 number:6 day:15 month:12 https://dx.doi.org/10.1186/bcr3076 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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_2005 GBV_ILN_2014 GBV_ILN_2106 GBV_ILN_2232 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 13 2011 6 15 12
allfieldsGer	10.1186/bcr3076 doi (DE-627)SPR029944953 (SPR)bcr3076-e DE-627 ger DE-627 rakwb eng Heikkinen, Tuomas verfasserin aut Variants on the promoter region of PTEN affect breast cancer progression and patient survival 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Heikkinen et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( Introduction The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer. Methods We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes. Results All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets. Conclusions Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer. Breast Cancer (dpeaa)DE-He213 PTEN Expression (dpeaa)DE-He213 PTEN Gene (dpeaa)DE-He213 Distant Metastasis Free Survival (dpeaa)DE-He213 Promoter Variant (dpeaa)DE-He213 Greco, Dario aut Pelttari, Liisa M aut Tommiska, Johanna aut Vahteristo, Pia aut Heikkilä, Päivi aut Blomqvist, Carl aut Aittomäki, Kristiina aut Nevanlinna, Heli aut Enthalten in Breast cancer research London : BioMed Central, 1999 13(2011), 6 vom: 15. Dez. (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:13 year:2011 number:6 day:15 month:12 https://dx.doi.org/10.1186/bcr3076 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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_2005 GBV_ILN_2014 GBV_ILN_2106 GBV_ILN_2232 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 13 2011 6 15 12
allfieldsSound	10.1186/bcr3076 doi (DE-627)SPR029944953 (SPR)bcr3076-e DE-627 ger DE-627 rakwb eng Heikkinen, Tuomas verfasserin aut Variants on the promoter region of PTEN affect breast cancer progression and patient survival 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Heikkinen et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( Introduction The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer. Methods We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes. Results All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets. Conclusions Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer. Breast Cancer (dpeaa)DE-He213 PTEN Expression (dpeaa)DE-He213 PTEN Gene (dpeaa)DE-He213 Distant Metastasis Free Survival (dpeaa)DE-He213 Promoter Variant (dpeaa)DE-He213 Greco, Dario aut Pelttari, Liisa M aut Tommiska, Johanna aut Vahteristo, Pia aut Heikkilä, Päivi aut Blomqvist, Carl aut Aittomäki, Kristiina aut Nevanlinna, Heli aut Enthalten in Breast cancer research London : BioMed Central, 1999 13(2011), 6 vom: 15. Dez. (DE-627)326645950 (DE-600)2041618-0 1465-542X nnns volume:13 year:2011 number:6 day:15 month:12 https://dx.doi.org/10.1186/bcr3076 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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_2005 GBV_ILN_2014 GBV_ILN_2106 GBV_ILN_2232 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 13 2011 6 15 12
language	English
source	Enthalten in Breast cancer research 13(2011), 6 vom: 15. Dez. volume:13 year:2011 number:6 day:15 month:12
sourceStr	Enthalten in Breast cancer research 13(2011), 6 vom: 15. Dez. volume:13 year:2011 number:6 day:15 month:12
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Breast Cancer PTEN Expression PTEN Gene Distant Metastasis Free Survival Promoter Variant
isfreeaccess_bool	true
container_title	Breast cancer research
authorswithroles_txt_mv	Heikkinen, Tuomas @@aut@@ Greco, Dario @@aut@@ Pelttari, Liisa M @@aut@@ Tommiska, Johanna @@aut@@ Vahteristo, Pia @@aut@@ Heikkilä, Päivi @@aut@@ Blomqvist, Carl @@aut@@ Aittomäki, Kristiina @@aut@@ Nevanlinna, Heli @@aut@@
publishDateDaySort_date	2011-12-15T00:00:00Z
hierarchy_top_id	326645950
id	SPR029944953
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR029944953</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519113832.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2011 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/bcr3076</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR029944953</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)bcr3076-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Heikkinen, Tuomas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Variants on the promoter region of PTEN affect breast cancer progression and patient survival</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2011</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="500" ind1=" " ind2=" "><subfield code="a">© Heikkinen et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Introduction The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer. Methods We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes. Results All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets. Conclusions Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Breast Cancer</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">PTEN Expression</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">PTEN Gene</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Distant Metastasis Free Survival</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Promoter Variant</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Greco, Dario</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Pelttari, Liisa M</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tommiska, Johanna</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Vahteristo, Pia</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Heikkilä, Päivi</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Blomqvist, Carl</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Aittomäki, Kristiina</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Nevanlinna, Heli</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Breast cancer research</subfield><subfield code="d">London : BioMed Central, 1999</subfield><subfield code="g">13(2011), 6 vom: 15. Dez.</subfield><subfield code="w">(DE-627)326645950</subfield><subfield code="w">(DE-600)2041618-0</subfield><subfield code="x">1465-542X</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:13</subfield><subfield code="g">year:2011</subfield><subfield code="g">number:6</subfield><subfield code="g">day:15</subfield><subfield code="g">month:12</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1186/bcr3076</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2106</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2232</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">13</subfield><subfield code="j">2011</subfield><subfield code="e">6</subfield><subfield code="b">15</subfield><subfield code="c">12</subfield></datafield></record></collection>
author	Heikkinen, Tuomas
spellingShingle	Heikkinen, Tuomas misc Breast Cancer misc PTEN Expression misc PTEN Gene misc Distant Metastasis Free Survival misc Promoter Variant Variants on the promoter region of PTEN affect breast cancer progression and patient survival
authorStr	Heikkinen, Tuomas
ppnlink_with_tag_str_mv	@@773@@(DE-627)326645950
format	electronic Article
delete_txt_mv	keep
author_role	aut aut aut aut aut aut aut aut aut
collection	springer
remote_str	true
illustrated	Not Illustrated
issn	1465-542X
topic_title	Variants on the promoter region of PTEN affect breast cancer progression and patient survival Breast Cancer (dpeaa)DE-He213 PTEN Expression (dpeaa)DE-He213 PTEN Gene (dpeaa)DE-He213 Distant Metastasis Free Survival (dpeaa)DE-He213 Promoter Variant (dpeaa)DE-He213
topic	misc Breast Cancer misc PTEN Expression misc PTEN Gene misc Distant Metastasis Free Survival misc Promoter Variant
topic_unstemmed	misc Breast Cancer misc PTEN Expression misc PTEN Gene misc Distant Metastasis Free Survival misc Promoter Variant
topic_browse	misc Breast Cancer misc PTEN Expression misc PTEN Gene misc Distant Metastasis Free Survival misc Promoter Variant
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
format_main_str_mv	Text Zeitschrift/Artikel
carriertype_str_mv	cr
hierarchy_parent_title	Breast cancer research
hierarchy_parent_id	326645950
hierarchy_top_title	Breast cancer research
isfreeaccess_txt	true
familylinks_str_mv	(DE-627)326645950 (DE-600)2041618-0
title	Variants on the promoter region of PTEN affect breast cancer progression and patient survival
ctrlnum	(DE-627)SPR029944953 (SPR)bcr3076-e
title_full	Variants on the promoter region of PTEN affect breast cancer progression and patient survival
author_sort	Heikkinen, Tuomas
journal	Breast cancer research
journalStr	Breast cancer research
lang_code	eng
isOA_bool	true
recordtype	marc
publishDateSort	2011
contenttype_str_mv	txt
author_browse	Heikkinen, Tuomas Greco, Dario Pelttari, Liisa M Tommiska, Johanna Vahteristo, Pia Heikkilä, Päivi Blomqvist, Carl Aittomäki, Kristiina Nevanlinna, Heli
container_volume	13
format_se	Elektronische Aufsätze
author-letter	Heikkinen, Tuomas
doi_str_mv	10.1186/bcr3076
title_sort	variants on the promoter region of pten affect breast cancer progression and patient survival
title_auth	Variants on the promoter region of PTEN affect breast cancer progression and patient survival
abstract	Introduction The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer. Methods We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes. Results All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets. Conclusions Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer. © Heikkinen et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (
abstractGer	Introduction The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer. Methods We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes. Results All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets. Conclusions Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer. © Heikkinen et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (
abstract_unstemmed	Introduction The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer. Methods We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes. Results All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets. Conclusions Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer. © Heikkinen et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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_2005 GBV_ILN_2014 GBV_ILN_2106 GBV_ILN_2232 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
container_issue	6
title_short	Variants on the promoter region of PTEN affect breast cancer progression and patient survival
url	https://dx.doi.org/10.1186/bcr3076
remote_bool	true
author2	Greco, Dario Pelttari, Liisa M Tommiska, Johanna Vahteristo, Pia Heikkilä, Päivi Blomqvist, Carl Aittomäki, Kristiina Nevanlinna, Heli
author2Str	Greco, Dario Pelttari, Liisa M Tommiska, Johanna Vahteristo, Pia Heikkilä, Päivi Blomqvist, Carl Aittomäki, Kristiina Nevanlinna, Heli
ppnlink	326645950
mediatype_str_mv	c
isOA_txt	true
hochschulschrift_bool	false
doi_str	10.1186/bcr3076
up_date	2024-07-04T02:46:41.753Z
_version_	1803614894691450880
fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR029944953</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519113832.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2011 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/bcr3076</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR029944953</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)bcr3076-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Heikkinen, Tuomas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Variants on the promoter region of PTEN affect breast cancer progression and patient survival</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2011</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="500" ind1=" " ind2=" "><subfield code="a">© Heikkinen et al.; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Introduction The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer. Methods We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes. Results All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets. Conclusions Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Breast Cancer</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">PTEN Expression</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">PTEN Gene</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Distant Metastasis Free Survival</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Promoter Variant</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Greco, Dario</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Pelttari, Liisa M</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tommiska, Johanna</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Vahteristo, Pia</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Heikkilä, Päivi</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Blomqvist, Carl</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Aittomäki, Kristiina</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Nevanlinna, Heli</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Breast cancer research</subfield><subfield code="d">London : BioMed Central, 1999</subfield><subfield code="g">13(2011), 6 vom: 15. Dez.</subfield><subfield code="w">(DE-627)326645950</subfield><subfield code="w">(DE-600)2041618-0</subfield><subfield code="x">1465-542X</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:13</subfield><subfield code="g">year:2011</subfield><subfield code="g">number:6</subfield><subfield code="g">day:15</subfield><subfield code="g">month:12</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1186/bcr3076</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2106</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2232</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">13</subfield><subfield code="j">2011</subfield><subfield code="e">6</subfield><subfield code="b">15</subfield><subfield code="c">12</subfield></datafield></record></collection>
score	7.399314

Nicht das Richtige dabei?

Schreiben Sie uns!

Variants on the promoter region of PTEN affect breast cancer progression and patient survival

Nicht das Richtige dabei?

Zugang & Verfügbarkeit

Vorhandene Bände

Nicht das Richtige dabei?