Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastoma

Autores
Torbidoni, Ana Vanesa; Laurent, Viviana Eunice; Sampor, Claudia; Ottaviani, Daniela; Vazquez, Valeria; Gabri, Mariano Rolando; Vazquez Rossi, Jorge Eduardo; Garcia de Davila, Maria Teresa; Alonso, Cristina; Alonso, Daniel Fernando; Chantada, Guillermo Luis
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
IMPORTANCE: Disseminated retinoblastoma is usually fatal. Identification of small amounts (minimal dissemination [MD]) of tumor cells in extraocular sites might be a tool for designing appropriate treatments. OBJECTIVE: To test cone-rod homeobox (CRX) transcription factor as a lineage-specific molecular marker for metastatic retinoblastoma and for evaluation of MD. DESIGN, SETTING, AND PARTICIPANTS: In a prospective cohort design study, we evaluated CRX messenger RNA (mRNA) by retrotranscription followed by real-time polymerase chain reaction as a diagnostic test in samples obtained from bone marrow, peripheral blood, and cerebrospinal fluid (CSF) at diagnosis, after induction chemotherapy, and during follow-up. The study was conducted from June 30, 2008, to June 30, 2014. Seventeen retinoblastoma primary tumors, 2 retinoblastoma cell lines, and 47 samples of bone marrow from other cancers (controls) were studied. Seventeen patients with metastatic retinoblastoma (9 at diagnosis, 8 at relapse; age range: 18-41 months) were included. MAIN OUTCOMES AND MEASURES: Detection of CRX mRNA as a marker for metastatic retinoblastoma and MD in bone marrow and CSF and its correlation with clinical findings. RESULTS: Cone-rod homeobox mRNA was expressed in all tumors (relative expression levels range, 8.1 × 10-5 to 5.6) and cell lines. In control samples, there was no amplification of CRX; only the housekeeping gene (GAPDH) demonstrated amplification. Bone marrow metastatic cells showed expression of CRX mRNA in all 9 children presenting with metastasis at the diagnosis (relative expression levels, 6.0 × 10-5 to 0.67). After induction chemotherapy, no evidence of MD of tumor cells was seen in any of the 8 responding children since only GAPDH showed amplification. In the CSF of children who had a metastatic relapse, CRX mRNA detection was positive in 2 patients in whom no conclusive results were reached by immunocytology for disialoganglioside GD2. Minimal dissemination in the CSF was associated with a clinical relapse in 2 cases. No concomitant MD was evident in the bone marrow in any case. CONCLUSIONS AND RELEVANCE: These data suggest that CRX mRNA is a novel marker for retinoblastoma at extraocular sites. In this study among patients with bone marrow metastasis, there was a quick, complete, and sustained molecular response after induction chemotherapy. In all patients with secondary metastasis, CSF relapse occurred independently from the bone marrow, suggesting a sanctuary site.
Fil: Torbidoni, Ana Vanesa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Laurent, Viviana Eunice. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Ottaviani, Daniela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Vazquez, Valeria. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Vazquez Rossi, Jorge Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Garcia de Davila, Maria Teresa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Alonso, Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Materia
Retinoblastoma
Minimal Disease
Cone-Rod Homeobox Transcription Factor
Real Time Pcr
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:11336/38631
Acceder
id CONICETDig_ddae496af4c36779f4df47784512e7cf
oai_identifier_str oai:ri.conicet.gov.ar:11336/38631
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastomaTorbidoni, Ana VanesaLaurent, Viviana EuniceSampor, ClaudiaOttaviani, DanielaVazquez, ValeriaGabri, Mariano RolandoVazquez Rossi, Jorge EduardoGarcia de Davila, Maria TeresaAlonso, CristinaAlonso, Daniel FernandoChantada, Guillermo LuisRetinoblastomaMinimal DiseaseCone-Rod Homeobox Transcription FactorReal Time Pcrhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3IMPORTANCE: Disseminated retinoblastoma is usually fatal. Identification of small amounts (minimal dissemination [MD]) of tumor cells in extraocular sites might be a tool for designing appropriate treatments. OBJECTIVE: To test cone-rod homeobox (CRX) transcription factor as a lineage-specific molecular marker for metastatic retinoblastoma and for evaluation of MD. DESIGN, SETTING, AND PARTICIPANTS: In a prospective cohort design study, we evaluated CRX messenger RNA (mRNA) by retrotranscription followed by real-time polymerase chain reaction as a diagnostic test in samples obtained from bone marrow, peripheral blood, and cerebrospinal fluid (CSF) at diagnosis, after induction chemotherapy, and during follow-up. The study was conducted from June 30, 2008, to June 30, 2014. Seventeen retinoblastoma primary tumors, 2 retinoblastoma cell lines, and 47 samples of bone marrow from other cancers (controls) were studied. Seventeen patients with metastatic retinoblastoma (9 at diagnosis, 8 at relapse; age range: 18-41 months) were included. MAIN OUTCOMES AND MEASURES: Detection of CRX mRNA as a marker for metastatic retinoblastoma and MD in bone marrow and CSF and its correlation with clinical findings. RESULTS: Cone-rod homeobox mRNA was expressed in all tumors (relative expression levels range, 8.1 × 10-5 to 5.6) and cell lines. In control samples, there was no amplification of CRX; only the housekeeping gene (GAPDH) demonstrated amplification. Bone marrow metastatic cells showed expression of CRX mRNA in all 9 children presenting with metastasis at the diagnosis (relative expression levels, 6.0 × 10-5 to 0.67). After induction chemotherapy, no evidence of MD of tumor cells was seen in any of the 8 responding children since only GAPDH showed amplification. In the CSF of children who had a metastatic relapse, CRX mRNA detection was positive in 2 patients in whom no conclusive results were reached by immunocytology for disialoganglioside GD2. Minimal dissemination in the CSF was associated with a clinical relapse in 2 cases. No concomitant MD was evident in the bone marrow in any case. CONCLUSIONS AND RELEVANCE: These data suggest that CRX mRNA is a novel marker for retinoblastoma at extraocular sites. In this study among patients with bone marrow metastasis, there was a quick, complete, and sustained molecular response after induction chemotherapy. In all patients with secondary metastasis, CSF relapse occurred independently from the bone marrow, suggesting a sanctuary site.Fil: Torbidoni, Ana Vanesa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Laurent, Viviana Eunice. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Ottaviani, Daniela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Vazquez, Valeria. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Vazquez Rossi, Jorge Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Garcia de Davila, Maria Teresa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Alonso, Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaAmerican Medical Association2015-07info: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/11336/38631Torbidoni, Ana Vanesa; Laurent, Viviana Eunice; Sampor, Claudia; Ottaviani, Daniela; Vazquez, Valeria; et al.; Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastoma; American Medical Association; JAMA Ophthalmology; 133; 7; 7-2015; 805-8122168-6165CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1001/jamaophthalmol.2015.0900info:eu-repo/semantics/altIdentifier/url/https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2276935info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-29T12:28:33Zoai:ri.conicet.gov.ar:11336/38631instacron: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:34982025-10-29 12:28:34.176CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastoma
title Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastoma
spellingShingle Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastoma
Torbidoni, Ana Vanesa
Retinoblastoma
Minimal Disease
Cone-Rod Homeobox Transcription Factor
Real Time Pcr
title_short Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastoma
title_full Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastoma
title_fullStr Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastoma
title_full_unstemmed Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastoma
title_sort Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastoma
dc.creator.none.fl_str_mv Torbidoni, Ana Vanesa
Laurent, Viviana Eunice
Sampor, Claudia
Ottaviani, Daniela
Vazquez, Valeria
Gabri, Mariano Rolando
Vazquez Rossi, Jorge Eduardo
Garcia de Davila, Maria Teresa
Alonso, Cristina
Alonso, Daniel Fernando
Chantada, Guillermo Luis
author Torbidoni, Ana Vanesa
author_facet Torbidoni, Ana Vanesa
Laurent, Viviana Eunice
Sampor, Claudia
Ottaviani, Daniela
Vazquez, Valeria
Gabri, Mariano Rolando
Vazquez Rossi, Jorge Eduardo
Garcia de Davila, Maria Teresa
Alonso, Cristina
Alonso, Daniel Fernando
Chantada, Guillermo Luis
author_role author
author2 Laurent, Viviana Eunice
Sampor, Claudia
Ottaviani, Daniela
Vazquez, Valeria
Gabri, Mariano Rolando
Vazquez Rossi, Jorge Eduardo
Garcia de Davila, Maria Teresa
Alonso, Cristina
Alonso, Daniel Fernando
Chantada, Guillermo Luis
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Retinoblastoma
Minimal Disease
Cone-Rod Homeobox Transcription Factor
Real Time Pcr
topic Retinoblastoma
Minimal Disease
Cone-Rod Homeobox Transcription Factor
Real Time Pcr
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv IMPORTANCE: Disseminated retinoblastoma is usually fatal. Identification of small amounts (minimal dissemination [MD]) of tumor cells in extraocular sites might be a tool for designing appropriate treatments. OBJECTIVE: To test cone-rod homeobox (CRX) transcription factor as a lineage-specific molecular marker for metastatic retinoblastoma and for evaluation of MD. DESIGN, SETTING, AND PARTICIPANTS: In a prospective cohort design study, we evaluated CRX messenger RNA (mRNA) by retrotranscription followed by real-time polymerase chain reaction as a diagnostic test in samples obtained from bone marrow, peripheral blood, and cerebrospinal fluid (CSF) at diagnosis, after induction chemotherapy, and during follow-up. The study was conducted from June 30, 2008, to June 30, 2014. Seventeen retinoblastoma primary tumors, 2 retinoblastoma cell lines, and 47 samples of bone marrow from other cancers (controls) were studied. Seventeen patients with metastatic retinoblastoma (9 at diagnosis, 8 at relapse; age range: 18-41 months) were included. MAIN OUTCOMES AND MEASURES: Detection of CRX mRNA as a marker for metastatic retinoblastoma and MD in bone marrow and CSF and its correlation with clinical findings. RESULTS: Cone-rod homeobox mRNA was expressed in all tumors (relative expression levels range, 8.1 × 10-5 to 5.6) and cell lines. In control samples, there was no amplification of CRX; only the housekeeping gene (GAPDH) demonstrated amplification. Bone marrow metastatic cells showed expression of CRX mRNA in all 9 children presenting with metastasis at the diagnosis (relative expression levels, 6.0 × 10-5 to 0.67). After induction chemotherapy, no evidence of MD of tumor cells was seen in any of the 8 responding children since only GAPDH showed amplification. In the CSF of children who had a metastatic relapse, CRX mRNA detection was positive in 2 patients in whom no conclusive results were reached by immunocytology for disialoganglioside GD2. Minimal dissemination in the CSF was associated with a clinical relapse in 2 cases. No concomitant MD was evident in the bone marrow in any case. CONCLUSIONS AND RELEVANCE: These data suggest that CRX mRNA is a novel marker for retinoblastoma at extraocular sites. In this study among patients with bone marrow metastasis, there was a quick, complete, and sustained molecular response after induction chemotherapy. In all patients with secondary metastasis, CSF relapse occurred independently from the bone marrow, suggesting a sanctuary site.
Fil: Torbidoni, Ana Vanesa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Laurent, Viviana Eunice. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Ottaviani, Daniela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Vazquez, Valeria. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Vazquez Rossi, Jorge Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Garcia de Davila, Maria Teresa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Alonso, Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
description IMPORTANCE: Disseminated retinoblastoma is usually fatal. Identification of small amounts (minimal dissemination [MD]) of tumor cells in extraocular sites might be a tool for designing appropriate treatments. OBJECTIVE: To test cone-rod homeobox (CRX) transcription factor as a lineage-specific molecular marker for metastatic retinoblastoma and for evaluation of MD. DESIGN, SETTING, AND PARTICIPANTS: In a prospective cohort design study, we evaluated CRX messenger RNA (mRNA) by retrotranscription followed by real-time polymerase chain reaction as a diagnostic test in samples obtained from bone marrow, peripheral blood, and cerebrospinal fluid (CSF) at diagnosis, after induction chemotherapy, and during follow-up. The study was conducted from June 30, 2008, to June 30, 2014. Seventeen retinoblastoma primary tumors, 2 retinoblastoma cell lines, and 47 samples of bone marrow from other cancers (controls) were studied. Seventeen patients with metastatic retinoblastoma (9 at diagnosis, 8 at relapse; age range: 18-41 months) were included. MAIN OUTCOMES AND MEASURES: Detection of CRX mRNA as a marker for metastatic retinoblastoma and MD in bone marrow and CSF and its correlation with clinical findings. RESULTS: Cone-rod homeobox mRNA was expressed in all tumors (relative expression levels range, 8.1 × 10-5 to 5.6) and cell lines. In control samples, there was no amplification of CRX; only the housekeeping gene (GAPDH) demonstrated amplification. Bone marrow metastatic cells showed expression of CRX mRNA in all 9 children presenting with metastasis at the diagnosis (relative expression levels, 6.0 × 10-5 to 0.67). After induction chemotherapy, no evidence of MD of tumor cells was seen in any of the 8 responding children since only GAPDH showed amplification. In the CSF of children who had a metastatic relapse, CRX mRNA detection was positive in 2 patients in whom no conclusive results were reached by immunocytology for disialoganglioside GD2. Minimal dissemination in the CSF was associated with a clinical relapse in 2 cases. No concomitant MD was evident in the bone marrow in any case. CONCLUSIONS AND RELEVANCE: These data suggest that CRX mRNA is a novel marker for retinoblastoma at extraocular sites. In this study among patients with bone marrow metastasis, there was a quick, complete, and sustained molecular response after induction chemotherapy. In all patients with secondary metastasis, CSF relapse occurred independently from the bone marrow, suggesting a sanctuary site.
publishDate 2015
dc.date.none.fl_str_mv 2015-07
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/11336/38631
Torbidoni, Ana Vanesa; Laurent, Viviana Eunice; Sampor, Claudia; Ottaviani, Daniela; Vazquez, Valeria; et al.; Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastoma; American Medical Association; JAMA Ophthalmology; 133; 7; 7-2015; 805-812
2168-6165
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38631
identifier_str_mv Torbidoni, Ana Vanesa; Laurent, Viviana Eunice; Sampor, Claudia; Ottaviani, Daniela; Vazquez, Valeria; et al.; Association of cone-rod homeobox transcription factor messenger RNA with pediatric metastatic retinoblastoma; American Medical Association; JAMA Ophthalmology; 133; 7; 7-2015; 805-812
2168-6165
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1001/jamaophthalmol.2015.0900
info:eu-repo/semantics/altIdentifier/url/https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2276935
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 Medical Association
publisher.none.fl_str_mv American Medical Association
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
_version_ 1847427216940466176
score 12.589754

Publicaciones similares