Epigenetic laterality differences in breast cancer

Autores
Masuelli, Sofía; Roque Moreno, Maria
Año de publicación
2019
Idioma
español castellano
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Breast Cancer is a heterogeneous disease. By previous studies we determined that mammary tumors of left-right sides (L-R) differ in their behavior as inferred from their methylation profiles. Normal breast L-R tissues have not identical environments; they differ in size, irrigation and fat composition. It is also known that epigenetics functions as a bridge between environment and gene expression. Our hypothesis sustains that L-R tumors differ in epigenetically regulated pathways, provoked by the diverse L-R microenvironment. To study this, we performed in-silico and invivo analyses. From database c-BioPortal Provisional Breast Cancer, 708 tumors with information for 16.000 genes were included and L-R methylation medias were compared for each gene. The top 169 genes with significant L-R difference above 3% were selected (T test, p<0.0001) and filtered by cancer related search terms in Metascape. Fifty three genes were associated with the terms “inflammation”, “proliferation negative regulation”, “immune response”, “DNA damage response”, “P53 pathway”, “angiogenesis”, “migration”, “cell death regulation”, “survival” and “apoptosis”. Then, the methylation profiles were converted into the 7 cancer terms. Interestingly, the cancer term profiles clustered into 2 groups associated with L-R laterality (Hierarchical cluster analysis, bootstrap 90-100 %), suggesting the existence of different L-R methylation profiles associated with functional terms. In the invivo studies, the methylome of 6 L-R xenografts generated by inoculation of MDA-MB231 cells in NSG mice were analyzed by RRBS. Preliminary analyses reveal 197 gene promoters, with significant L-R difference (FDR corrected p<0.01). Further functional and expression studies will allow to evaluate the impact of these methylation differences on the tumor behavior. So far, our studies support an interesting epigenetic related laterality hypothesis for breast cancer, which could serve as proof of principle for other bilateral tumors.
Fil: Masuelli, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Roque Moreno, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Reunión anual de Sociedades de Biociencia; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología XXXI; Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicina; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Materia
LATERALIDAD
CANCER
MAMA
EPIGENETICA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/230744

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network_name_str CONICET Digital (CONICET)
spelling Epigenetic laterality differences in breast cancerMasuelli, SofíaRoque Moreno, MariaLATERALIDADCANCERMAMAEPIGENETICAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Breast Cancer is a heterogeneous disease. By previous studies we determined that mammary tumors of left-right sides (L-R) differ in their behavior as inferred from their methylation profiles. Normal breast L-R tissues have not identical environments; they differ in size, irrigation and fat composition. It is also known that epigenetics functions as a bridge between environment and gene expression. Our hypothesis sustains that L-R tumors differ in epigenetically regulated pathways, provoked by the diverse L-R microenvironment. To study this, we performed in-silico and invivo analyses. From database c-BioPortal Provisional Breast Cancer, 708 tumors with information for 16.000 genes were included and L-R methylation medias were compared for each gene. The top 169 genes with significant L-R difference above 3% were selected (T test, p<0.0001) and filtered by cancer related search terms in Metascape. Fifty three genes were associated with the terms “inflammation”, “proliferation negative regulation”, “immune response”, “DNA damage response”, “P53 pathway”, “angiogenesis”, “migration”, “cell death regulation”, “survival” and “apoptosis”. Then, the methylation profiles were converted into the 7 cancer terms. Interestingly, the cancer term profiles clustered into 2 groups associated with L-R laterality (Hierarchical cluster analysis, bootstrap 90-100 %), suggesting the existence of different L-R methylation profiles associated with functional terms. In the invivo studies, the methylome of 6 L-R xenografts generated by inoculation of MDA-MB231 cells in NSG mice were analyzed by RRBS. Preliminary analyses reveal 197 gene promoters, with significant L-R difference (FDR corrected p<0.01). Further functional and expression studies will allow to evaluate the impact of these methylation differences on the tumor behavior. So far, our studies support an interesting epigenetic related laterality hypothesis for breast cancer, which could serve as proof of principle for other bilateral tumors.Fil: Masuelli, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Roque Moreno, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaReunión anual de Sociedades de Biociencia; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología XXXI; Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicina; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioFundación Revista MedicinaCostas, Monica AlejandraMarino, Gabriela InésAzurmendi, Pablo Javier2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/230744Epigenetic laterality differences in breast cancer; Reunión anual de Sociedades de Biociencia; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología XXXI; Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicina; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 149-1490025-7680CONICET DigitalCONICETspainfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:33:07Zoai:ri.conicet.gov.ar:11336/230744instacron: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:34982025-09-29 10:33:07.814CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Epigenetic laterality differences in breast cancer
title Epigenetic laterality differences in breast cancer
spellingShingle Epigenetic laterality differences in breast cancer
Masuelli, Sofía
LATERALIDAD
CANCER
MAMA
EPIGENETICA
title_short Epigenetic laterality differences in breast cancer
title_full Epigenetic laterality differences in breast cancer
title_fullStr Epigenetic laterality differences in breast cancer
title_full_unstemmed Epigenetic laterality differences in breast cancer
title_sort Epigenetic laterality differences in breast cancer
dc.creator.none.fl_str_mv Masuelli, Sofía
Roque Moreno, Maria
author Masuelli, Sofía
author_facet Masuelli, Sofía
Roque Moreno, Maria
author_role author
author2 Roque Moreno, Maria
author2_role author
dc.contributor.none.fl_str_mv Costas, Monica Alejandra
Marino, Gabriela Inés
Azurmendi, Pablo Javier
dc.subject.none.fl_str_mv LATERALIDAD
CANCER
MAMA
EPIGENETICA
topic LATERALIDAD
CANCER
MAMA
EPIGENETICA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Breast Cancer is a heterogeneous disease. By previous studies we determined that mammary tumors of left-right sides (L-R) differ in their behavior as inferred from their methylation profiles. Normal breast L-R tissues have not identical environments; they differ in size, irrigation and fat composition. It is also known that epigenetics functions as a bridge between environment and gene expression. Our hypothesis sustains that L-R tumors differ in epigenetically regulated pathways, provoked by the diverse L-R microenvironment. To study this, we performed in-silico and invivo analyses. From database c-BioPortal Provisional Breast Cancer, 708 tumors with information for 16.000 genes were included and L-R methylation medias were compared for each gene. The top 169 genes with significant L-R difference above 3% were selected (T test, p<0.0001) and filtered by cancer related search terms in Metascape. Fifty three genes were associated with the terms “inflammation”, “proliferation negative regulation”, “immune response”, “DNA damage response”, “P53 pathway”, “angiogenesis”, “migration”, “cell death regulation”, “survival” and “apoptosis”. Then, the methylation profiles were converted into the 7 cancer terms. Interestingly, the cancer term profiles clustered into 2 groups associated with L-R laterality (Hierarchical cluster analysis, bootstrap 90-100 %), suggesting the existence of different L-R methylation profiles associated with functional terms. In the invivo studies, the methylome of 6 L-R xenografts generated by inoculation of MDA-MB231 cells in NSG mice were analyzed by RRBS. Preliminary analyses reveal 197 gene promoters, with significant L-R difference (FDR corrected p<0.01). Further functional and expression studies will allow to evaluate the impact of these methylation differences on the tumor behavior. So far, our studies support an interesting epigenetic related laterality hypothesis for breast cancer, which could serve as proof of principle for other bilateral tumors.
Fil: Masuelli, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Roque Moreno, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Reunión anual de Sociedades de Biociencia; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología XXXI; Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicina; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
description Breast Cancer is a heterogeneous disease. By previous studies we determined that mammary tumors of left-right sides (L-R) differ in their behavior as inferred from their methylation profiles. Normal breast L-R tissues have not identical environments; they differ in size, irrigation and fat composition. It is also known that epigenetics functions as a bridge between environment and gene expression. Our hypothesis sustains that L-R tumors differ in epigenetically regulated pathways, provoked by the diverse L-R microenvironment. To study this, we performed in-silico and invivo analyses. From database c-BioPortal Provisional Breast Cancer, 708 tumors with information for 16.000 genes were included and L-R methylation medias were compared for each gene. The top 169 genes with significant L-R difference above 3% were selected (T test, p<0.0001) and filtered by cancer related search terms in Metascape. Fifty three genes were associated with the terms “inflammation”, “proliferation negative regulation”, “immune response”, “DNA damage response”, “P53 pathway”, “angiogenesis”, “migration”, “cell death regulation”, “survival” and “apoptosis”. Then, the methylation profiles were converted into the 7 cancer terms. Interestingly, the cancer term profiles clustered into 2 groups associated with L-R laterality (Hierarchical cluster analysis, bootstrap 90-100 %), suggesting the existence of different L-R methylation profiles associated with functional terms. In the invivo studies, the methylome of 6 L-R xenografts generated by inoculation of MDA-MB231 cells in NSG mice were analyzed by RRBS. Preliminary analyses reveal 197 gene promoters, with significant L-R difference (FDR corrected p<0.01). Further functional and expression studies will allow to evaluate the impact of these methylation differences on the tumor behavior. So far, our studies support an interesting epigenetic related laterality hypothesis for breast cancer, which could serve as proof of principle for other bilateral tumors.
publishDate 2019
dc.date.none.fl_str_mv 2019
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Epigenetic laterality differences in breast cancer; Reunión anual de Sociedades de Biociencia; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología XXXI; Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicina; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 149-149
0025-7680
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identifier_str_mv Epigenetic laterality differences in breast cancer; Reunión anual de Sociedades de Biociencia; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología XXXI; Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicina; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 149-149
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