Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame dele...
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Autor*in:	Abate, Francesco [verfasserIn] da Silva-Almeida, Ana C Zairis, Sakellarios Robles-Valero, Javier Couronne, Lucile Khiabanian, Hossein Quinn, S. Aidan Kim, Mi-Yeon Laginestra, Maria Antonella Kim, Christine Fiore, Danilo Bhagat, Govind Piris, Miguel Angel Campo, Elias Lossos, Izidore S Bernard, Olivier A Inghirami, Giorgio Pileri, Stefano Bustelo, Xosé R Rabadan, Raul Ferrando, Adolfo A Palomero, Teresa

Format:	Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	Genetics Lymphomas Lymphocytes Medical prognosis Pathogenesis

Übergeordnetes Werk:	Enthalten in: Proceedings of the National Academy of Sciences of the United States of America - Washington, DC : NAS, 1877, 114(2017), 4, Seite 764-769
Übergeordnetes Werk:	volume:114 ; year:2017 ; number:4 ; pages:764-769

Links:	Volltext Link aufrufen

DOI / URN:	10.1073/pnas.1608839114

Katalog-ID:	OLC1989962742

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520			\|a Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways. These results support a driver oncogenic role for VAV1 signaling in the pathogenesis of PTCL.
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700	1		\|a Couronne, Lucile \|4 oth
700	1		\|a Khiabanian, Hossein \|4 oth
700	1		\|a Quinn, S. Aidan \|4 oth
700	1		\|a Kim, Mi-Yeon \|4 oth
700	1		\|a Laginestra, Maria Antonella \|4 oth
700	1		\|a Kim, Christine \|4 oth
700	1		\|a Fiore, Danilo \|4 oth
700	1		\|a Bhagat, Govind \|4 oth
700	1		\|a Piris, Miguel Angel \|4 oth
700	1		\|a Campo, Elias \|4 oth
700	1		\|a Lossos, Izidore S \|4 oth
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700	1		\|a Pileri, Stefano \|4 oth
700	1		\|a Bustelo, Xosé R \|4 oth
700	1		\|a Rabadan, Raul \|4 oth
700	1		\|a Ferrando, Adolfo A \|4 oth
700	1		\|a Palomero, Teresa \|4 oth
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allfields	10.1073/pnas.1608839114 doi PQ20170206 (DE-627)OLC1989962742 (DE-599)GBVOLC1989962742 (PRQ)c686-9f0991bbb2b9833a7f8a90f3405f9b69f25c6c8601d6ba7803492ced05dd3f870 (KEY)0583363920170000114000400764activatingmutationsandtranslocationsintheguanineex DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Abate, Francesco verfasserin aut Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways. These results support a driver oncogenic role for VAV1 signaling in the pathogenesis of PTCL. Genetics Lymphomas Lymphocytes Medical prognosis Pathogenesis da Silva-Almeida, Ana C oth Zairis, Sakellarios oth Robles-Valero, Javier oth Couronne, Lucile oth Khiabanian, Hossein oth Quinn, S. Aidan oth Kim, Mi-Yeon oth Laginestra, Maria Antonella oth Kim, Christine oth Fiore, Danilo oth Bhagat, Govind oth Piris, Miguel Angel oth Campo, Elias oth Lossos, Izidore S oth Bernard, Olivier A oth Inghirami, Giorgio oth Pileri, Stefano oth Bustelo, Xosé R oth Rabadan, Raul oth Ferrando, Adolfo A oth Palomero, Teresa oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 4, Seite 764-769 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:4 pages:764-769 http://dx.doi.org/10.1073/pnas.1608839114 Volltext http://search.proquest.com/docview/1862662026 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 4 764-769
spelling	10.1073/pnas.1608839114 doi PQ20170206 (DE-627)OLC1989962742 (DE-599)GBVOLC1989962742 (PRQ)c686-9f0991bbb2b9833a7f8a90f3405f9b69f25c6c8601d6ba7803492ced05dd3f870 (KEY)0583363920170000114000400764activatingmutationsandtranslocationsintheguanineex DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Abate, Francesco verfasserin aut Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways. These results support a driver oncogenic role for VAV1 signaling in the pathogenesis of PTCL. Genetics Lymphomas Lymphocytes Medical prognosis Pathogenesis da Silva-Almeida, Ana C oth Zairis, Sakellarios oth Robles-Valero, Javier oth Couronne, Lucile oth Khiabanian, Hossein oth Quinn, S. Aidan oth Kim, Mi-Yeon oth Laginestra, Maria Antonella oth Kim, Christine oth Fiore, Danilo oth Bhagat, Govind oth Piris, Miguel Angel oth Campo, Elias oth Lossos, Izidore S oth Bernard, Olivier A oth Inghirami, Giorgio oth Pileri, Stefano oth Bustelo, Xosé R oth Rabadan, Raul oth Ferrando, Adolfo A oth Palomero, Teresa oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 4, Seite 764-769 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:4 pages:764-769 http://dx.doi.org/10.1073/pnas.1608839114 Volltext http://search.proquest.com/docview/1862662026 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 4 764-769
allfields_unstemmed	10.1073/pnas.1608839114 doi PQ20170206 (DE-627)OLC1989962742 (DE-599)GBVOLC1989962742 (PRQ)c686-9f0991bbb2b9833a7f8a90f3405f9b69f25c6c8601d6ba7803492ced05dd3f870 (KEY)0583363920170000114000400764activatingmutationsandtranslocationsintheguanineex DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Abate, Francesco verfasserin aut Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways. These results support a driver oncogenic role for VAV1 signaling in the pathogenesis of PTCL. Genetics Lymphomas Lymphocytes Medical prognosis Pathogenesis da Silva-Almeida, Ana C oth Zairis, Sakellarios oth Robles-Valero, Javier oth Couronne, Lucile oth Khiabanian, Hossein oth Quinn, S. Aidan oth Kim, Mi-Yeon oth Laginestra, Maria Antonella oth Kim, Christine oth Fiore, Danilo oth Bhagat, Govind oth Piris, Miguel Angel oth Campo, Elias oth Lossos, Izidore S oth Bernard, Olivier A oth Inghirami, Giorgio oth Pileri, Stefano oth Bustelo, Xosé R oth Rabadan, Raul oth Ferrando, Adolfo A oth Palomero, Teresa oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 4, Seite 764-769 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:4 pages:764-769 http://dx.doi.org/10.1073/pnas.1608839114 Volltext http://search.proquest.com/docview/1862662026 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 4 764-769
allfieldsGer	10.1073/pnas.1608839114 doi PQ20170206 (DE-627)OLC1989962742 (DE-599)GBVOLC1989962742 (PRQ)c686-9f0991bbb2b9833a7f8a90f3405f9b69f25c6c8601d6ba7803492ced05dd3f870 (KEY)0583363920170000114000400764activatingmutationsandtranslocationsintheguanineex DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Abate, Francesco verfasserin aut Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways. These results support a driver oncogenic role for VAV1 signaling in the pathogenesis of PTCL. Genetics Lymphomas Lymphocytes Medical prognosis Pathogenesis da Silva-Almeida, Ana C oth Zairis, Sakellarios oth Robles-Valero, Javier oth Couronne, Lucile oth Khiabanian, Hossein oth Quinn, S. Aidan oth Kim, Mi-Yeon oth Laginestra, Maria Antonella oth Kim, Christine oth Fiore, Danilo oth Bhagat, Govind oth Piris, Miguel Angel oth Campo, Elias oth Lossos, Izidore S oth Bernard, Olivier A oth Inghirami, Giorgio oth Pileri, Stefano oth Bustelo, Xosé R oth Rabadan, Raul oth Ferrando, Adolfo A oth Palomero, Teresa oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 4, Seite 764-769 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:4 pages:764-769 http://dx.doi.org/10.1073/pnas.1608839114 Volltext http://search.proquest.com/docview/1862662026 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 4 764-769
allfieldsSound	10.1073/pnas.1608839114 doi PQ20170206 (DE-627)OLC1989962742 (DE-599)GBVOLC1989962742 (PRQ)c686-9f0991bbb2b9833a7f8a90f3405f9b69f25c6c8601d6ba7803492ced05dd3f870 (KEY)0583363920170000114000400764activatingmutationsandtranslocationsintheguanineex DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Abate, Francesco verfasserin aut Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways. These results support a driver oncogenic role for VAV1 signaling in the pathogenesis of PTCL. Genetics Lymphomas Lymphocytes Medical prognosis Pathogenesis da Silva-Almeida, Ana C oth Zairis, Sakellarios oth Robles-Valero, Javier oth Couronne, Lucile oth Khiabanian, Hossein oth Quinn, S. Aidan oth Kim, Mi-Yeon oth Laginestra, Maria Antonella oth Kim, Christine oth Fiore, Danilo oth Bhagat, Govind oth Piris, Miguel Angel oth Campo, Elias oth Lossos, Izidore S oth Bernard, Olivier A oth Inghirami, Giorgio oth Pileri, Stefano oth Bustelo, Xosé R oth Rabadan, Raul oth Ferrando, Adolfo A oth Palomero, Teresa oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 4, Seite 764-769 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:4 pages:764-769 http://dx.doi.org/10.1073/pnas.1608839114 Volltext http://search.proquest.com/docview/1862662026 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 4 764-769
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source	Enthalten in Proceedings of the National Academy of Sciences of the United States of America 114(2017), 4, Seite 764-769 volume:114 year:2017 number:4 pages:764-769
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topic_facet	Genetics Lymphomas Lymphocytes Medical prognosis Pathogenesis
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container_title	Proceedings of the National Academy of Sciences of the United States of America
authorswithroles_txt_mv	Abate, Francesco @@aut@@ da Silva-Almeida, Ana C @@oth@@ Zairis, Sakellarios @@oth@@ Robles-Valero, Javier @@oth@@ Couronne, Lucile @@oth@@ Khiabanian, Hossein @@oth@@ Quinn, S. Aidan @@oth@@ Kim, Mi-Yeon @@oth@@ Laginestra, Maria Antonella @@oth@@ Kim, Christine @@oth@@ Fiore, Danilo @@oth@@ Bhagat, Govind @@oth@@ Piris, Miguel Angel @@oth@@ Campo, Elias @@oth@@ Lossos, Izidore S @@oth@@ Bernard, Olivier A @@oth@@ Inghirami, Giorgio @@oth@@ Pileri, Stefano @@oth@@ Bustelo, Xosé R @@oth@@ Rabadan, Raul @@oth@@ Ferrando, Adolfo A @@oth@@ Palomero, Teresa @@oth@@
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author	Abate, Francesco
spellingShingle	Abate, Francesco ddc 500 ddc 570 fid LING fid BIODIV misc Genetics misc Lymphomas misc Lymphocytes misc Medical prognosis misc Pathogenesis Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
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topic_title	500 DNB 570 AVZ LING fid BIODIV fid Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas Genetics Lymphomas Lymphocytes Medical prognosis Pathogenesis
topic	ddc 500 ddc 570 fid LING fid BIODIV misc Genetics misc Lymphomas misc Lymphocytes misc Medical prognosis misc Pathogenesis
topic_unstemmed	ddc 500 ddc 570 fid LING fid BIODIV misc Genetics misc Lymphomas misc Lymphocytes misc Medical prognosis misc Pathogenesis
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title	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
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title_full	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
author_sort	Abate, Francesco
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title_sort	activating mutations and translocations in the guanine exchange factor vav1 in peripheral t-cell lymphomas
title_auth	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
abstract	Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways. These results support a driver oncogenic role for VAV1 signaling in the pathogenesis of PTCL.
abstractGer	Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways. These results support a driver oncogenic role for VAV1 signaling in the pathogenesis of PTCL.
abstract_unstemmed	Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways. These results support a driver oncogenic role for VAV1 signaling in the pathogenesis of PTCL.
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container_issue	4
title_short	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
url	http://dx.doi.org/10.1073/pnas.1608839114 http://search.proquest.com/docview/1862662026
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doi_str	10.1073/pnas.1608839114
up_date	2024-07-03T23:23:51.018Z
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