Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival

Mateos Manteca, María Victoria; García Sanz, Ramón; López‐Pérez, Ricardo; Moro, Maria J.; Ocio San Miguel, Enrique M.; Hernández, José; Megido, Marta; Caballero, Maria D.; Fernández‐Calvo, Javier; Bárez, Abelardo; Almeida Parra, Julia María; Orfao de Matos Correia e Vale, José Alberto; González, Marcos; San Miguel Izquierdo, Jesús Fernando

Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival

[EN]In order to gain further insights into the role of the p16 gene in cell cycle regulation and the prognostic implications of its inactivation, we investigated the methylation status of the p16 gene in 98 untreated patients using a polymerase chain reaction assay based on the inability of some res...

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Autores:	Mateos Manteca, María Victoria, García Sanz, Ramón, López‐Pérez, Ricardo, Moro, Maria J., Ocio San Miguel, Enrique M., Hernández, José, Megido, Marta, Caballero, Maria D., Fernández‐Calvo, Javier, Bárez, Abelardo, Almeida Parra, Julia María, Orfao de Matos Correia e Vale, José Alberto, González, Marcos, San Miguel Izquierdo, Jesús Fernando
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2002
País:	España
Institución:	Universidad de Salamanca (USAL)
Repositorio:	GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:	oai:gredos.usal.es:10366/154612
Acceso en línea:	http://hdl.handle.net/10366/154612
Access Level:	acceso embargado
Palabra clave:	Mieloma múltiple Multiple Myeloma mieloma múltiple

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spelling	Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survivalMateos Manteca, María VictoriaGarcía Sanz, RamónLópez‐Pérez, RicardoMoro, Maria J.Ocio San Miguel, Enrique M.Hernández, JoséMegido, MartaCaballero, Maria D.Fernández‐Calvo, JavierBárez, AbelardoAlmeida Parra, Julia MaríaOrfao de Matos Correia e Vale, José AlbertoGonzález, MarcosSan Miguel Izquierdo, Jesús FernandoMieloma múltipleMultiple Myelomamieloma múltiple[EN]In order to gain further insights into the role of the p16 gene in cell cycle regulation and the prognostic implications of its inactivation, we investigated the methylation status of the p16 gene in 98 untreated patients using a polymerase chain reaction assay based on the inability of some restriction enzymes to digest methylated sequences. Forty-one patients showed a p16 methylated gene (42%). The percentage of S-phase plasma cells (PC) in these patients was almost three times higher than in those with an unmethylated p16 gene (4Æ16% ± 3Æ37% vs 1Æ5% ± 1Æ41%, P < 0Æ001). The presence of p16 methylation also correlated with both elevated b2-microglobulin serum levels and high C-reactive protein values. Patients with a p16 methylated gene had shorter overall and progression-free survival than those patients without p16 methylation. However, this feature did not retain independent prognostic influence on multivariate analysis, probably due to its association with the S-phase PC, which had more potent statistical significance in the Cox model. These findings showed methylation of the p16 gene was a frequent event in MM patients at diagnosis, and was associated with an increased proliferative rate of plasma cells and a poor prognosis, indicating an important role for p16 gene in the cell cycle regulation of multiple myeloma tumour cells, and thus in the clinical outcome of the disease.Wileyinfo202420242002info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10366/154612reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)Inglésinfo:eu-repo/semantics/embargoedAccessoai:gredos.usal.es:10366/1546122026-06-07T06:28:51Z
dc.title.none.fl_str_mv	Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival
title	Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival
spellingShingle	Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival Mateos Manteca, María Victoria Mieloma múltiple Multiple Myeloma mieloma múltiple
title_short	Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival
title_full	Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival
title_fullStr	Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival
title_full_unstemmed	Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival
title_sort	Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival
dc.creator.none.fl_str_mv	Mateos Manteca, María Victoria García Sanz, Ramón López‐Pérez, Ricardo Moro, Maria J. Ocio San Miguel, Enrique M. Hernández, José Megido, Marta Caballero, Maria D. Fernández‐Calvo, Javier Bárez, Abelardo Almeida Parra, Julia María Orfao de Matos Correia e Vale, José Alberto González, Marcos San Miguel Izquierdo, Jesús Fernando
author	Mateos Manteca, María Victoria
author_facet	Mateos Manteca, María Victoria García Sanz, Ramón López‐Pérez, Ricardo Moro, Maria J. Ocio San Miguel, Enrique M. Hernández, José Megido, Marta Caballero, Maria D. Fernández‐Calvo, Javier Bárez, Abelardo Almeida Parra, Julia María Orfao de Matos Correia e Vale, José Alberto González, Marcos San Miguel Izquierdo, Jesús Fernando
author_role	author
author2	García Sanz, Ramón López‐Pérez, Ricardo Moro, Maria J. Ocio San Miguel, Enrique M. Hernández, José Megido, Marta Caballero, Maria D. Fernández‐Calvo, Javier Bárez, Abelardo Almeida Parra, Julia María Orfao de Matos Correia e Vale, José Alberto González, Marcos San Miguel Izquierdo, Jesús Fernando
author2_role	author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Mieloma múltiple Multiple Myeloma mieloma múltiple
topic	Mieloma múltiple Multiple Myeloma mieloma múltiple
description	[EN]In order to gain further insights into the role of the p16 gene in cell cycle regulation and the prognostic implications of its inactivation, we investigated the methylation status of the p16 gene in 98 untreated patients using a polymerase chain reaction assay based on the inability of some restriction enzymes to digest methylated sequences. Forty-one patients showed a p16 methylated gene (42%). The percentage of S-phase plasma cells (PC) in these patients was almost three times higher than in those with an unmethylated p16 gene (4Æ16% ± 3Æ37% vs 1Æ5% ± 1Æ41%, P < 0Æ001). The presence of p16 methylation also correlated with both elevated b2-microglobulin serum levels and high C-reactive protein values. Patients with a p16 methylated gene had shorter overall and progression-free survival than those patients without p16 methylation. However, this feature did not retain independent prognostic influence on multivariate analysis, probably due to its association with the S-phase PC, which had more potent statistical significance in the Cox model. These findings showed methylation of the p16 gene was a frequent event in MM patients at diagnosis, and was associated with an increased proliferative rate of plasma cells and a poor prognosis, indicating an important role for p16 gene in the cell cycle regulation of multiple myeloma tumour cells, and thus in the clinical outcome of the disease.
publishDate	2002
dc.date.none.fl_str_mv	2002 2024 2024 info
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10366/154612
url	http://hdl.handle.net/10366/154612
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.rights.none.fl_str_mv	info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv	embargoedAccess
dc.publisher.none.fl_str_mv	Wiley
publisher.none.fl_str_mv	Wiley
dc.source.none.fl_str_mv	reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca instname:Universidad de Salamanca (USAL)
instname_str	Universidad de Salamanca (USAL)
reponame_str	GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection	GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,300724

Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival

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