Working together for the family: Determination of HER oncogene co-amplifications in breast cancer

Autores
Laurito, Sergio Roberto; Branham, Maria Teresita; Campoy, Emanuel Martin; Real Varela, Sebastián Martín; Cueto, Juan Agustin; Urrutia, Guillermo; Gago, Francisco Eduardo; Tello, Olga; Glatstein, Telma Beatriz; De la Iglesia, Paola; Atanesyan, Lilit; Savola, Suvi; Roque Moreno, Maria
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
HER2 is a well-studied tyrosine kinase (TK) membrane receptor which functions as a therapeutic target in invasive ductal breast carcinomas (IDC). The standard of care for the treatment of HER2-positive breast is the antibody trastuzumab. Despite specific treatment unfortunately, 20% of primary and 70% of metastatic HER2 tumors develop resistance. HER2 belongs to a gene family, with four members (HER1-4) and these members could be involved in resistance to anti-HER2 therapies. In this study we designed a probemix to detect the amplification of the four HER oncogenes in a single reaction. In addition, we developed a protocol based on the combination of MLPA with ddPCR to detect the tumor proportion of co-amplified HERs. On 111 IDC, the HER2 MLPA results were validated by FISH (Adjusted r2 = 0,91, p < 0,0001), CISH (Adjusted r2 = 0,938, p < 0,0001) and IHC (Adjusted r2 = 0,31, p < 0,0001). HER1-4 MLPA results were validated by RT-qPCR assays (Spearman Rank test p < 0,05). Of the 111 samples, 26% presented at least one HER amplified, of which 23% showed co-amplifications with other HERs. The percentage of cells with HER2 co-amplified varied among the tumors (from 2-72,6%). Independent in-silico findings show that the outcome of HER2+ patients is conditioned by the status of HER3 and HER4. Our results encourage further studies to investigate the relationship with patient's response to single or combined treatment. The approach could serve as proof of principle for other tumors in which the HER oncogenes are involved.
Fil: Laurito, Sergio Roberto. 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: Branham, Maria Teresita. 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: Campoy, Emanuel Martin. 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: Real Varela, Sebastián Martín. 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: Cueto, Juan Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Urrutia, Guillermo. Medical College Of Wisconsin; Estados Unidos
Fil: Gago, Francisco Eduardo. No especifíca;
Fil: Tello, Olga. No especifíca;
Fil: Glatstein, Telma Beatriz. No especifíca;
Fil: De la Iglesia, Paola. Hospital Italiano; Argentina
Fil: Atanesyan, Lilit. MRC-Holland BV, Department of Oncogenetics, Amsterdam; Países Bajos
Fil: Savola, Suvi. No especifíca;
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
Materia
BREAST CANCER
CO-AMPLIFICATION
DIGITAL PCR
HER ONCOGENES
MLPA
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:11336/141423
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/141423
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Working together for the family: Determination of HER oncogene co-amplifications in breast cancerLaurito, Sergio RobertoBranham, Maria TeresitaCampoy, Emanuel MartinReal Varela, Sebastián MartínCueto, Juan AgustinUrrutia, GuillermoGago, Francisco EduardoTello, OlgaGlatstein, Telma BeatrizDe la Iglesia, PaolaAtanesyan, LilitSavola, SuviRoque Moreno, MariaBREAST CANCERCO-AMPLIFICATIONDIGITAL PCRHER ONCOGENESMLPAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1HER2 is a well-studied tyrosine kinase (TK) membrane receptor which functions as a therapeutic target in invasive ductal breast carcinomas (IDC). The standard of care for the treatment of HER2-positive breast is the antibody trastuzumab. Despite specific treatment unfortunately, 20% of primary and 70% of metastatic HER2 tumors develop resistance. HER2 belongs to a gene family, with four members (HER1-4) and these members could be involved in resistance to anti-HER2 therapies. In this study we designed a probemix to detect the amplification of the four HER oncogenes in a single reaction. In addition, we developed a protocol based on the combination of MLPA with ddPCR to detect the tumor proportion of co-amplified HERs. On 111 IDC, the HER2 MLPA results were validated by FISH (Adjusted r2 = 0,91, p < 0,0001), CISH (Adjusted r2 = 0,938, p < 0,0001) and IHC (Adjusted r2 = 0,31, p < 0,0001). HER1-4 MLPA results were validated by RT-qPCR assays (Spearman Rank test p < 0,05). Of the 111 samples, 26% presented at least one HER amplified, of which 23% showed co-amplifications with other HERs. The percentage of cells with HER2 co-amplified varied among the tumors (from 2-72,6%). Independent in-silico findings show that the outcome of HER2+ patients is conditioned by the status of HER3 and HER4. Our results encourage further studies to investigate the relationship with patient's response to single or combined treatment. The approach could serve as proof of principle for other tumors in which the HER oncogenes are involved.Fil: Laurito, Sergio Roberto. 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: Branham, Maria Teresita. 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: Campoy, Emanuel Martin. 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: Real Varela, Sebastián Martín. 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: Cueto, Juan Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Urrutia, Guillermo. Medical College Of Wisconsin; Estados UnidosFil: Gago, Francisco Eduardo. No especifíca;Fil: Tello, Olga. No especifíca;Fil: Glatstein, Telma Beatriz. No especifíca;Fil: De la Iglesia, Paola. Hospital Italiano; ArgentinaFil: Atanesyan, Lilit. MRC-Holland BV, Department of Oncogenetics, Amsterdam; Países BajosFil: Savola, Suvi. No especifíca;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; ArgentinaImpact Journals2020-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/141423Laurito, Sergio Roberto; Branham, Maria Teresita; Campoy, Emanuel Martin; Real Varela, Sebastián Martín; Cueto, Juan Agustin; et al.; Working together for the family: Determination of HER oncogene co-amplifications in breast cancer; Impact Journals; Oncotarget; 11; 28; 7-2020; 2774-27921949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/article/27671/text/info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.27671info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:37:09Zoai:ri.conicet.gov.ar:11336/141423instacron: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 09:37:09.517CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Working together for the family: Determination of HER oncogene co-amplifications in breast cancer
title Working together for the family: Determination of HER oncogene co-amplifications in breast cancer
spellingShingle Working together for the family: Determination of HER oncogene co-amplifications in breast cancer
Laurito, Sergio Roberto
BREAST CANCER
CO-AMPLIFICATION
DIGITAL PCR
HER ONCOGENES
MLPA
title_short Working together for the family: Determination of HER oncogene co-amplifications in breast cancer
title_full Working together for the family: Determination of HER oncogene co-amplifications in breast cancer
title_fullStr Working together for the family: Determination of HER oncogene co-amplifications in breast cancer
title_full_unstemmed Working together for the family: Determination of HER oncogene co-amplifications in breast cancer
title_sort Working together for the family: Determination of HER oncogene co-amplifications in breast cancer
dc.creator.none.fl_str_mv Laurito, Sergio Roberto
Branham, Maria Teresita
Campoy, Emanuel Martin
Real Varela, Sebastián Martín
Cueto, Juan Agustin
Urrutia, Guillermo
Gago, Francisco Eduardo
Tello, Olga
Glatstein, Telma Beatriz
De la Iglesia, Paola
Atanesyan, Lilit
Savola, Suvi
Roque Moreno, Maria
author Laurito, Sergio Roberto
author_facet Laurito, Sergio Roberto
Branham, Maria Teresita
Campoy, Emanuel Martin
Real Varela, Sebastián Martín
Cueto, Juan Agustin
Urrutia, Guillermo
Gago, Francisco Eduardo
Tello, Olga
Glatstein, Telma Beatriz
De la Iglesia, Paola
Atanesyan, Lilit
Savola, Suvi
Roque Moreno, Maria
author_role author
author2 Branham, Maria Teresita
Campoy, Emanuel Martin
Real Varela, Sebastián Martín
Cueto, Juan Agustin
Urrutia, Guillermo
Gago, Francisco Eduardo
Tello, Olga
Glatstein, Telma Beatriz
De la Iglesia, Paola
Atanesyan, Lilit
Savola, Suvi
Roque Moreno, Maria
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BREAST CANCER
CO-AMPLIFICATION
DIGITAL PCR
HER ONCOGENES
MLPA
topic BREAST CANCER
CO-AMPLIFICATION
DIGITAL PCR
HER ONCOGENES
MLPA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv HER2 is a well-studied tyrosine kinase (TK) membrane receptor which functions as a therapeutic target in invasive ductal breast carcinomas (IDC). The standard of care for the treatment of HER2-positive breast is the antibody trastuzumab. Despite specific treatment unfortunately, 20% of primary and 70% of metastatic HER2 tumors develop resistance. HER2 belongs to a gene family, with four members (HER1-4) and these members could be involved in resistance to anti-HER2 therapies. In this study we designed a probemix to detect the amplification of the four HER oncogenes in a single reaction. In addition, we developed a protocol based on the combination of MLPA with ddPCR to detect the tumor proportion of co-amplified HERs. On 111 IDC, the HER2 MLPA results were validated by FISH (Adjusted r2 = 0,91, p < 0,0001), CISH (Adjusted r2 = 0,938, p < 0,0001) and IHC (Adjusted r2 = 0,31, p < 0,0001). HER1-4 MLPA results were validated by RT-qPCR assays (Spearman Rank test p < 0,05). Of the 111 samples, 26% presented at least one HER amplified, of which 23% showed co-amplifications with other HERs. The percentage of cells with HER2 co-amplified varied among the tumors (from 2-72,6%). Independent in-silico findings show that the outcome of HER2+ patients is conditioned by the status of HER3 and HER4. Our results encourage further studies to investigate the relationship with patient's response to single or combined treatment. The approach could serve as proof of principle for other tumors in which the HER oncogenes are involved.
Fil: Laurito, Sergio Roberto. 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: Branham, Maria Teresita. 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: Campoy, Emanuel Martin. 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: Real Varela, Sebastián Martín. 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: Cueto, Juan Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Urrutia, Guillermo. Medical College Of Wisconsin; Estados Unidos
Fil: Gago, Francisco Eduardo. No especifíca;
Fil: Tello, Olga. No especifíca;
Fil: Glatstein, Telma Beatriz. No especifíca;
Fil: De la Iglesia, Paola. Hospital Italiano; Argentina
Fil: Atanesyan, Lilit. MRC-Holland BV, Department of Oncogenetics, Amsterdam; Países Bajos
Fil: Savola, Suvi. No especifíca;
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
description HER2 is a well-studied tyrosine kinase (TK) membrane receptor which functions as a therapeutic target in invasive ductal breast carcinomas (IDC). The standard of care for the treatment of HER2-positive breast is the antibody trastuzumab. Despite specific treatment unfortunately, 20% of primary and 70% of metastatic HER2 tumors develop resistance. HER2 belongs to a gene family, with four members (HER1-4) and these members could be involved in resistance to anti-HER2 therapies. In this study we designed a probemix to detect the amplification of the four HER oncogenes in a single reaction. In addition, we developed a protocol based on the combination of MLPA with ddPCR to detect the tumor proportion of co-amplified HERs. On 111 IDC, the HER2 MLPA results were validated by FISH (Adjusted r2 = 0,91, p < 0,0001), CISH (Adjusted r2 = 0,938, p < 0,0001) and IHC (Adjusted r2 = 0,31, p < 0,0001). HER1-4 MLPA results were validated by RT-qPCR assays (Spearman Rank test p < 0,05). Of the 111 samples, 26% presented at least one HER amplified, of which 23% showed co-amplifications with other HERs. The percentage of cells with HER2 co-amplified varied among the tumors (from 2-72,6%). Independent in-silico findings show that the outcome of HER2+ patients is conditioned by the status of HER3 and HER4. Our results encourage further studies to investigate the relationship with patient's response to single or combined treatment. The approach could serve as proof of principle for other tumors in which the HER oncogenes are involved.
publishDate 2020
dc.date.none.fl_str_mv 2020-07
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/11336/141423
Laurito, Sergio Roberto; Branham, Maria Teresita; Campoy, Emanuel Martin; Real Varela, Sebastián Martín; Cueto, Juan Agustin; et al.; Working together for the family: Determination of HER oncogene co-amplifications in breast cancer; Impact Journals; Oncotarget; 11; 28; 7-2020; 2774-2792
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/141423
identifier_str_mv Laurito, Sergio Roberto; Branham, Maria Teresita; Campoy, Emanuel Martin; Real Varela, Sebastián Martín; Cueto, Juan Agustin; et al.; Working together for the family: Determination of HER oncogene co-amplifications in breast cancer; Impact Journals; Oncotarget; 11; 28; 7-2020; 2774-2792
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/article/27671/text/
info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.27671
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
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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