Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations
- Autores
- Ottaviani, Daniela; Parma, Diana Lidia; Ferrer, Marcela Maria; Giliberto, Florencia; Luce, Leonela Natalia; Alonso, Cristina; Szijan, Irena
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background: Retinoblastoma, the most common ocular cancer of childhood, is caused by inactivation of the RB1 tumor suppressor gene in the developing retina. It may occur as unilateral, bilateral or rarely as multicentric retinoblastoma, including pineal or suprasellar tumors. Being the retinoblastoma a hereditary cancer, identification of the causative mutation is important for risk prediction in the family members. An early detection of tumor is critical for survival and eye preservation. Screening for RB1 mutations is important for early tumor detection, critical for survival and eye preservation. Purpose: To identify causative RB1 mutations in retinoblastoma patients with different clinical presentations, some of them with a rare multicentric retinoblastoma or with a second non ocular malignancy, as well as the rare association with down syndrome. A comprehensive approach was used to identify the mutations and to detect children with a hereditary condition. Methods: A cohort of 20 patients with unilateral, bilateral and multicentric retinoblastoma was studied. Blood and tumor DNA was analyzed by sequencing, segregation of polymorphisms and MLPA analyses. Some of the rare mutations were validated by cloning or by Real-Time PCR. Results: Six germline and seven somatic mutations were identified; they include nonsense, frameshift, splice mutations and gross rearrangements, four of them novel. Three out of four nonsense/ frameshift germline mutations were associated with severe phenotype: bilateral and multicentric retinoblastomas. The at-riskhaplotype was identified in a familial case including one patient with osteosarcoma; it was useful for detection of mutation carriers. Conclusions: This study allowed us to identify causative RB1 mutations, including several novels. Some patients showed uncommon clinical presentations of retinoblastoma. These data are significant for genetic counseling. Our results support the relevance of carrying out complete genetic screening for RB1 mutations in both constitutional and tumor tissues.
Fil: Ottaviani, Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
Fil: Parma, Diana Lidia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Ferrer, Marcela Maria. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Florencia Giliberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
Fil: Luce, Leonela Natalia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
Fil: Alonso, Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina
Fil: Szijan, Irena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina - Materia
-
Retinoblastoma
Hereditary And Non Hereditary
Clinical Presentation
Rb1 Tumor Suppressor Gene
Rb1-Mutations
At-Riskhaplotype - 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:11336/30525
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Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical PresentationsOttaviani, DanielaParma, Diana LidiaFerrer, Marcela MariaGiliberto, FlorenciaLuce, Leonela NataliaAlonso, CristinaSzijan, IrenaRetinoblastomaHereditary And Non HereditaryClinical PresentationRb1 Tumor Suppressor GeneRb1-MutationsAt-Riskhaplotypehttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background: Retinoblastoma, the most common ocular cancer of childhood, is caused by inactivation of the RB1 tumor suppressor gene in the developing retina. It may occur as unilateral, bilateral or rarely as multicentric retinoblastoma, including pineal or suprasellar tumors. Being the retinoblastoma a hereditary cancer, identification of the causative mutation is important for risk prediction in the family members. An early detection of tumor is critical for survival and eye preservation. Screening for RB1 mutations is important for early tumor detection, critical for survival and eye preservation. Purpose: To identify causative RB1 mutations in retinoblastoma patients with different clinical presentations, some of them with a rare multicentric retinoblastoma or with a second non ocular malignancy, as well as the rare association with down syndrome. A comprehensive approach was used to identify the mutations and to detect children with a hereditary condition. Methods: A cohort of 20 patients with unilateral, bilateral and multicentric retinoblastoma was studied. Blood and tumor DNA was analyzed by sequencing, segregation of polymorphisms and MLPA analyses. Some of the rare mutations were validated by cloning or by Real-Time PCR. Results: Six germline and seven somatic mutations were identified; they include nonsense, frameshift, splice mutations and gross rearrangements, four of them novel. Three out of four nonsense/ frameshift germline mutations were associated with severe phenotype: bilateral and multicentric retinoblastomas. The at-riskhaplotype was identified in a familial case including one patient with osteosarcoma; it was useful for detection of mutation carriers. Conclusions: This study allowed us to identify causative RB1 mutations, including several novels. Some patients showed uncommon clinical presentations of retinoblastoma. These data are significant for genetic counseling. Our results support the relevance of carrying out complete genetic screening for RB1 mutations in both constitutional and tumor tissues.Fil: Ottaviani, Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Parma, Diana Lidia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Ferrer, Marcela Maria. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Florencia Giliberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Luce, Leonela Natalia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Alonso, Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; ArgentinaFil: Szijan, Irena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaSciTechnol2015-02info: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/11336/30525Ottaviani, Daniela; Parma, Diana Lidia; Ferrer, Marcela Maria; Giliberto, Florencia; Luce, Leonela Natalia; et al.; Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations; SciTechnol; Journal of Genetic Disorders and Genetic Reports; 4; 1; 2-2015; 1-72327-5790CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.4172/2327-5790.1000120info:eu-repo/semantics/altIdentifier/url/https://www.scitechnol.com/mutations-in-the-rb-gene-in-argentine-retinoblastoma-patients-and-uncommon-clinical-presentations-hFJ1.php?article_id=2615info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:54:12Zoai:ri.conicet.gov.ar:11336/30525instacron: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:34982025-09-03 09:54:13.089CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations |
title |
Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations |
spellingShingle |
Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations Ottaviani, Daniela Retinoblastoma Hereditary And Non Hereditary Clinical Presentation Rb1 Tumor Suppressor Gene Rb1-Mutations At-Riskhaplotype |
title_short |
Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations |
title_full |
Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations |
title_fullStr |
Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations |
title_full_unstemmed |
Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations |
title_sort |
Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations |
dc.creator.none.fl_str_mv |
Ottaviani, Daniela Parma, Diana Lidia Ferrer, Marcela Maria Giliberto, Florencia Luce, Leonela Natalia Alonso, Cristina Szijan, Irena |
author |
Ottaviani, Daniela |
author_facet |
Ottaviani, Daniela Parma, Diana Lidia Ferrer, Marcela Maria Giliberto, Florencia Luce, Leonela Natalia Alonso, Cristina Szijan, Irena |
author_role |
author |
author2 |
Parma, Diana Lidia Ferrer, Marcela Maria Giliberto, Florencia Luce, Leonela Natalia Alonso, Cristina Szijan, Irena |
author2_role |
author author author author author author |
dc.subject.none.fl_str_mv |
Retinoblastoma Hereditary And Non Hereditary Clinical Presentation Rb1 Tumor Suppressor Gene Rb1-Mutations At-Riskhaplotype |
topic |
Retinoblastoma Hereditary And Non Hereditary Clinical Presentation Rb1 Tumor Suppressor Gene Rb1-Mutations At-Riskhaplotype |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Background: Retinoblastoma, the most common ocular cancer of childhood, is caused by inactivation of the RB1 tumor suppressor gene in the developing retina. It may occur as unilateral, bilateral or rarely as multicentric retinoblastoma, including pineal or suprasellar tumors. Being the retinoblastoma a hereditary cancer, identification of the causative mutation is important for risk prediction in the family members. An early detection of tumor is critical for survival and eye preservation. Screening for RB1 mutations is important for early tumor detection, critical for survival and eye preservation. Purpose: To identify causative RB1 mutations in retinoblastoma patients with different clinical presentations, some of them with a rare multicentric retinoblastoma or with a second non ocular malignancy, as well as the rare association with down syndrome. A comprehensive approach was used to identify the mutations and to detect children with a hereditary condition. Methods: A cohort of 20 patients with unilateral, bilateral and multicentric retinoblastoma was studied. Blood and tumor DNA was analyzed by sequencing, segregation of polymorphisms and MLPA analyses. Some of the rare mutations were validated by cloning or by Real-Time PCR. Results: Six germline and seven somatic mutations were identified; they include nonsense, frameshift, splice mutations and gross rearrangements, four of them novel. Three out of four nonsense/ frameshift germline mutations were associated with severe phenotype: bilateral and multicentric retinoblastomas. The at-riskhaplotype was identified in a familial case including one patient with osteosarcoma; it was useful for detection of mutation carriers. Conclusions: This study allowed us to identify causative RB1 mutations, including several novels. Some patients showed uncommon clinical presentations of retinoblastoma. These data are significant for genetic counseling. Our results support the relevance of carrying out complete genetic screening for RB1 mutations in both constitutional and tumor tissues. Fil: Ottaviani, Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina Fil: Parma, Diana Lidia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Ferrer, Marcela Maria. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Florencia Giliberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina Fil: Luce, Leonela Natalia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina Fil: Alonso, Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina Fil: Szijan, Irena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina |
description |
Background: Retinoblastoma, the most common ocular cancer of childhood, is caused by inactivation of the RB1 tumor suppressor gene in the developing retina. It may occur as unilateral, bilateral or rarely as multicentric retinoblastoma, including pineal or suprasellar tumors. Being the retinoblastoma a hereditary cancer, identification of the causative mutation is important for risk prediction in the family members. An early detection of tumor is critical for survival and eye preservation. Screening for RB1 mutations is important for early tumor detection, critical for survival and eye preservation. Purpose: To identify causative RB1 mutations in retinoblastoma patients with different clinical presentations, some of them with a rare multicentric retinoblastoma or with a second non ocular malignancy, as well as the rare association with down syndrome. A comprehensive approach was used to identify the mutations and to detect children with a hereditary condition. Methods: A cohort of 20 patients with unilateral, bilateral and multicentric retinoblastoma was studied. Blood and tumor DNA was analyzed by sequencing, segregation of polymorphisms and MLPA analyses. Some of the rare mutations were validated by cloning or by Real-Time PCR. Results: Six germline and seven somatic mutations were identified; they include nonsense, frameshift, splice mutations and gross rearrangements, four of them novel. Three out of four nonsense/ frameshift germline mutations were associated with severe phenotype: bilateral and multicentric retinoblastomas. The at-riskhaplotype was identified in a familial case including one patient with osteosarcoma; it was useful for detection of mutation carriers. Conclusions: This study allowed us to identify causative RB1 mutations, including several novels. Some patients showed uncommon clinical presentations of retinoblastoma. These data are significant for genetic counseling. Our results support the relevance of carrying out complete genetic screening for RB1 mutations in both constitutional and tumor tissues. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-02 |
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/11336/30525 Ottaviani, Daniela; Parma, Diana Lidia; Ferrer, Marcela Maria; Giliberto, Florencia; Luce, Leonela Natalia; et al.; Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations; SciTechnol; Journal of Genetic Disorders and Genetic Reports; 4; 1; 2-2015; 1-7 2327-5790 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/30525 |
identifier_str_mv |
Ottaviani, Daniela; Parma, Diana Lidia; Ferrer, Marcela Maria; Giliberto, Florencia; Luce, Leonela Natalia; et al.; Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations; SciTechnol; Journal of Genetic Disorders and Genetic Reports; 4; 1; 2-2015; 1-7 2327-5790 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.4172/2327-5790.1000120 info:eu-repo/semantics/altIdentifier/url/https://www.scitechnol.com/mutations-in-the-rb-gene-in-argentine-retinoblastoma-patients-and-uncommon-clinical-presentations-hFJ1.php?article_id=2615 |
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/ |
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application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
SciTechnol |
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SciTechnol |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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