Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series

Autores: Anselmino, Nicolás; Labanca, Estefania; Shepherd, Peter D.A.; Dong, Jiabin; Yang, Ya Jung; Song, Xiaofei; Nandakumar, Subhiksha; Kundra, Ritika; Lee, Cindy; Schultz, Nikolaus; Zhang, Jianhua; Araujo, John C.; Aparicio, Ana M.; Subudhi, Sumit K.; Corn, Paul G.; Pisters, Louis L.; Ward, John F.; Davis, John W.; Vazquez, Elba Susana; Gueron, Geraldine; Logothetis, Christopher J.; Futreal, Andrew; Troncoso, Patricia; Chen, Yu; Navone, Nora M.
Año de publicación: 2024
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: Purpose: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer (PCa) models. This initiative builds on the rich MD Anderson (MDA) PCa patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal PCa. Experimental Design: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids. The cohort includes models derived from different morphologic groups, disease states, and involved organ sites (including circulating tumor cells), as well as paired samples representing heterogeneity or stages before and after therapy. Results: The cohort recapitulates clinically reported alterations in PCa genes, providing a data resource for clinical and molecular interrogation of suitable experimental models. Paired samples displayed conserved molecular alteration profiles, suggesting the relevance of other regulatory mechanisms (e.g., epigenomic) influenced by the microenvironment and/or treatment. Transcriptomically, models were grouped based on morphological classification. DNA damage response–associated mechanisms emerged as differentially regulated between adenocarcinoma and neuroendocrine PCa in a cross-interrogation of PDX/patient datasets. Conclusions:We addressed the gap in clinically relevant PCa models through comprehensive molecular characterization of MDA PCa PDXs, providing a discovery platform that integrates with patient data and benchmarked to therapeutically relevant consensus clinical groupings. This unique resource supports robust hypothesis generation and testing from basic, translational, and clinical perspectives.
Fil: Anselmino, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Labanca, Estefania. University of Texas; Estados Unidos
Fil: Shepherd, Peter D.A.. University of Texas; Estados Unidos
Fil: Dong, Jiabin. University of Texas; Estados Unidos
Fil: Yang, Ya Jung. University of Texas; Estados Unidos
Fil: Song, Xiaofei. University of Texas; Estados Unidos
Fil: Nandakumar, Subhiksha. No especifíca;
Fil: Kundra, Ritika. No especifíca;
Fil: Lee, Cindy. No especifíca;
Fil: Schultz, Nikolaus. Memorial Sloan Kettering Cancer Center; Estados Unidos
Fil: Zhang, Jianhua. University of Texas; Estados Unidos
Fil: Araujo, John C.. University of Texas; Estados Unidos
Fil: Aparicio, Ana M.. University of Texas; Estados Unidos
Fil: Subudhi, Sumit K.. University of Texas; Estados Unidos
Fil: Corn, Paul G.. University of Texas; Estados Unidos
Fil: Pisters, Louis L.. University of Texas; Estados Unidos
Fil: Ward, John F.. University of Texas; Estados Unidos
Fil: Davis, John W.. University of Texas; Estados Unidos
Fil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Gueron, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Logothetis, Christopher J.. University of Texas; Estados Unidos
Fil: Futreal, Andrew. University of Texas; Estados Unidos
Fil: Troncoso, Patricia. University of Texas; Estados Unidos
Fil: Chen, Yu. Weill Cornell Medical College; Estados Unidos
Fil: Navone, Nora M.. University of Texas; Estados Unidos
Materia: PDX
PROSTATE
CANCER
TRANSCRIPTOMICS
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
Institución: Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador: oai:ri.conicet.gov.ar:11336/276368

Acceder

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network_acronym_str	CONICETDig
repository_id_str	3498
network_name_str	CONICET Digital (CONICET)
spelling	Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) SeriesAnselmino, NicolásLabanca, EstefaniaShepherd, Peter D.A.Dong, JiabinYang, Ya JungSong, XiaofeiNandakumar, SubhikshaKundra, RitikaLee, CindySchultz, NikolausZhang, JianhuaAraujo, John C.Aparicio, Ana M.Subudhi, Sumit K.Corn, Paul G.Pisters, Louis L.Ward, John F.Davis, John W.Vazquez, Elba SusanaGueron, GeraldineLogothetis, Christopher J.Futreal, AndrewTroncoso, PatriciaChen, YuNavone, Nora M.PDXPROSTATECANCERTRANSCRIPTOMICShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Purpose: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer (PCa) models. This initiative builds on the rich MD Anderson (MDA) PCa patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal PCa. Experimental Design: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids. The cohort includes models derived from different morphologic groups, disease states, and involved organ sites (including circulating tumor cells), as well as paired samples representing heterogeneity or stages before and after therapy. Results: The cohort recapitulates clinically reported alterations in PCa genes, providing a data resource for clinical and molecular interrogation of suitable experimental models. Paired samples displayed conserved molecular alteration profiles, suggesting the relevance of other regulatory mechanisms (e.g., epigenomic) influenced by the microenvironment and/or treatment. Transcriptomically, models were grouped based on morphological classification. DNA damage response–associated mechanisms emerged as differentially regulated between adenocarcinoma and neuroendocrine PCa in a cross-interrogation of PDX/patient datasets. Conclusions:We addressed the gap in clinically relevant PCa models through comprehensive molecular characterization of MDA PCa PDXs, providing a discovery platform that integrates with patient data and benchmarked to therapeutically relevant consensus clinical groupings. This unique resource supports robust hypothesis generation and testing from basic, translational, and clinical perspectives.Fil: Anselmino, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Labanca, Estefania. University of Texas; Estados UnidosFil: Shepherd, Peter D.A.. University of Texas; Estados UnidosFil: Dong, Jiabin. University of Texas; Estados UnidosFil: Yang, Ya Jung. University of Texas; Estados UnidosFil: Song, Xiaofei. University of Texas; Estados UnidosFil: Nandakumar, Subhiksha. No especifíca;Fil: Kundra, Ritika. No especifíca;Fil: Lee, Cindy. No especifíca;Fil: Schultz, Nikolaus. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Zhang, Jianhua. University of Texas; Estados UnidosFil: Araujo, John C.. University of Texas; Estados UnidosFil: Aparicio, Ana M.. University of Texas; Estados UnidosFil: Subudhi, Sumit K.. University of Texas; Estados UnidosFil: Corn, Paul G.. University of Texas; Estados UnidosFil: Pisters, Louis L.. University of Texas; Estados UnidosFil: Ward, John F.. University of Texas; Estados UnidosFil: Davis, John W.. University of Texas; Estados UnidosFil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Gueron, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Logothetis, Christopher J.. University of Texas; Estados UnidosFil: Futreal, Andrew. University of Texas; Estados UnidosFil: Troncoso, Patricia. University of Texas; Estados UnidosFil: Chen, Yu. Weill Cornell Medical College; Estados UnidosFil: Navone, Nora M.. University of Texas; Estados UnidosAmerican Association for Cancer Research2024-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/276368Anselmino, Nicolás; Labanca, Estefania; Shepherd, Peter D.A.; Dong, Jiabin; Yang, Ya Jung; et al.; Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series; American Association for Cancer Research; Clinical Cancer Research; 30; 10; 3-2024; 2272-22851078-0432CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1158/1078-0432.CCR-23-2438info:eu-repo/semantics/altIdentifier/url/https://aacrjournals.org/clincancerres/article/30/10/2272/745168/Integrative-Molecular-Analyses-of-the-MD-Andersoninfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T14:37:05Zoai:ri.conicet.gov.ar:11336/276368instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-12-23 14:37:06.225CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv	Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
title	Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
spellingShingle	Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series Anselmino, Nicolás PDX PROSTATE CANCER TRANSCRIPTOMICS
title_short	Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
title_full	Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
title_fullStr	Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
title_full_unstemmed	Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
title_sort	Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
dc.creator.none.fl_str_mv	Anselmino, Nicolás Labanca, Estefania Shepherd, Peter D.A. Dong, Jiabin Yang, Ya Jung Song, Xiaofei Nandakumar, Subhiksha Kundra, Ritika Lee, Cindy Schultz, Nikolaus Zhang, Jianhua Araujo, John C. Aparicio, Ana M. Subudhi, Sumit K. Corn, Paul G. Pisters, Louis L. Ward, John F. Davis, John W. Vazquez, Elba Susana Gueron, Geraldine Logothetis, Christopher J. Futreal, Andrew Troncoso, Patricia Chen, Yu Navone, Nora M.
author	Anselmino, Nicolás
author_facet	Anselmino, Nicolás Labanca, Estefania Shepherd, Peter D.A. Dong, Jiabin Yang, Ya Jung Song, Xiaofei Nandakumar, Subhiksha Kundra, Ritika Lee, Cindy Schultz, Nikolaus Zhang, Jianhua Araujo, John C. Aparicio, Ana M. Subudhi, Sumit K. Corn, Paul G. Pisters, Louis L. Ward, John F. Davis, John W. Vazquez, Elba Susana Gueron, Geraldine Logothetis, Christopher J. Futreal, Andrew Troncoso, Patricia Chen, Yu Navone, Nora M.
author_role	author
author2	Labanca, Estefania Shepherd, Peter D.A. Dong, Jiabin Yang, Ya Jung Song, Xiaofei Nandakumar, Subhiksha Kundra, Ritika Lee, Cindy Schultz, Nikolaus Zhang, Jianhua Araujo, John C. Aparicio, Ana M. Subudhi, Sumit K. Corn, Paul G. Pisters, Louis L. Ward, John F. Davis, John W. Vazquez, Elba Susana Gueron, Geraldine Logothetis, Christopher J. Futreal, Andrew Troncoso, Patricia Chen, Yu Navone, Nora M.
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	PDX PROSTATE CANCER TRANSCRIPTOMICS
topic	PDX PROSTATE CANCER TRANSCRIPTOMICS
purl_subject.fl_str_mv	https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv	Purpose: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer (PCa) models. This initiative builds on the rich MD Anderson (MDA) PCa patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal PCa. Experimental Design: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids. The cohort includes models derived from different morphologic groups, disease states, and involved organ sites (including circulating tumor cells), as well as paired samples representing heterogeneity or stages before and after therapy. Results: The cohort recapitulates clinically reported alterations in PCa genes, providing a data resource for clinical and molecular interrogation of suitable experimental models. Paired samples displayed conserved molecular alteration profiles, suggesting the relevance of other regulatory mechanisms (e.g., epigenomic) influenced by the microenvironment and/or treatment. Transcriptomically, models were grouped based on morphological classification. DNA damage response–associated mechanisms emerged as differentially regulated between adenocarcinoma and neuroendocrine PCa in a cross-interrogation of PDX/patient datasets. Conclusions:We addressed the gap in clinically relevant PCa models through comprehensive molecular characterization of MDA PCa PDXs, providing a discovery platform that integrates with patient data and benchmarked to therapeutically relevant consensus clinical groupings. This unique resource supports robust hypothesis generation and testing from basic, translational, and clinical perspectives. Fil: Anselmino, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Labanca, Estefania. University of Texas; Estados Unidos Fil: Shepherd, Peter D.A.. University of Texas; Estados Unidos Fil: Dong, Jiabin. University of Texas; Estados Unidos Fil: Yang, Ya Jung. University of Texas; Estados Unidos Fil: Song, Xiaofei. University of Texas; Estados Unidos Fil: Nandakumar, Subhiksha. No especifíca; Fil: Kundra, Ritika. No especifíca; Fil: Lee, Cindy. No especifíca; Fil: Schultz, Nikolaus. Memorial Sloan Kettering Cancer Center; Estados Unidos Fil: Zhang, Jianhua. University of Texas; Estados Unidos Fil: Araujo, John C.. University of Texas; Estados Unidos Fil: Aparicio, Ana M.. University of Texas; Estados Unidos Fil: Subudhi, Sumit K.. University of Texas; Estados Unidos Fil: Corn, Paul G.. University of Texas; Estados Unidos Fil: Pisters, Louis L.. University of Texas; Estados Unidos Fil: Ward, John F.. University of Texas; Estados Unidos Fil: Davis, John W.. University of Texas; Estados Unidos Fil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Gueron, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Logothetis, Christopher J.. University of Texas; Estados Unidos Fil: Futreal, Andrew. University of Texas; Estados Unidos Fil: Troncoso, Patricia. University of Texas; Estados Unidos Fil: Chen, Yu. Weill Cornell Medical College; Estados Unidos Fil: Navone, Nora M.. University of Texas; Estados Unidos
description	Purpose: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer (PCa) models. This initiative builds on the rich MD Anderson (MDA) PCa patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal PCa. Experimental Design: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids. The cohort includes models derived from different morphologic groups, disease states, and involved organ sites (including circulating tumor cells), as well as paired samples representing heterogeneity or stages before and after therapy. Results: The cohort recapitulates clinically reported alterations in PCa genes, providing a data resource for clinical and molecular interrogation of suitable experimental models. Paired samples displayed conserved molecular alteration profiles, suggesting the relevance of other regulatory mechanisms (e.g., epigenomic) influenced by the microenvironment and/or treatment. Transcriptomically, models were grouped based on morphological classification. DNA damage response–associated mechanisms emerged as differentially regulated between adenocarcinoma and neuroendocrine PCa in a cross-interrogation of PDX/patient datasets. Conclusions:We addressed the gap in clinically relevant PCa models through comprehensive molecular characterization of MDA PCa PDXs, providing a discovery platform that integrates with patient data and benchmarked to therapeutically relevant consensus clinical groupings. This unique resource supports robust hypothesis generation and testing from basic, translational, and clinical perspectives.
publishDate	2024
dc.date.none.fl_str_mv	2024-03
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/11336/276368 Anselmino, Nicolás; Labanca, Estefania; Shepherd, Peter D.A.; Dong, Jiabin; Yang, Ya Jung; et al.; Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series; American Association for Cancer Research; Clinical Cancer Research; 30; 10; 3-2024; 2272-2285 1078-0432 CONICET Digital CONICET
url	http://hdl.handle.net/11336/276368
identifier_str_mv	Anselmino, Nicolás; Labanca, Estefania; Shepherd, Peter D.A.; Dong, Jiabin; Yang, Ya Jung; et al.; Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series; American Association for Cancer Research; Clinical Cancer Research; 30; 10; 3-2024; 2272-2285 1078-0432 CONICET Digital CONICET
dc.language.none.fl_str_mv	eng
language	eng
dc.relation.none.fl_str_mv	info:eu-repo/semantics/altIdentifier/doi/10.1158/1078-0432.CCR-23-2438 info:eu-repo/semantics/altIdentifier/url/https://aacrjournals.org/clincancerres/article/30/10/2272/745168/Integrative-Molecular-Analyses-of-the-MD-Anderson
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv	openAccess
rights_invalid_str_mv	https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv	application/pdf application/pdf application/pdf
dc.publisher.none.fl_str_mv	American Association for Cancer Research
publisher.none.fl_str_mv	American Association for Cancer Research
dc.source.none.fl_str_mv	reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str	CONICET Digital (CONICET)
collection	CONICET Digital (CONICET)
instname_str	Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv	CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv	dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score	12.441415

Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series

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