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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Oncología molecular > DA - CIMA - Oncología - Oncología molecular - Artículos de Revista >

Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas
Authors: Mestre-Escorihuela, C. (Cinta)
Rubio-Moscardo, F. (Fanny)
Richter, J.A. (José Ángel)
Siebert, R. (Reiner)
Climent, J. (J.)
Fresquet, V. (Vicente)
Beltran, E. (E.)
Aguirre, X. (Xavier)
Marugan, I. (Isabel)
Marin, M. (Miguel)
Rosenwald, A. (Andreas)
Sugimoto, K.J. (Kei-Ji)
Wheat, L.M. (Luise M.)
Karran, E. (E.L.)
Garcia, J. (José Francisco)
Sanchez, L. (Lydia)
Prosper, F. (Felipe)
Staudt, L.M. (Louis M.)
Pinkel, D. (Daniel)
Dyer, M. (M.J.S.)
Martinez-Climent, J.A. (José Angel)
Keywords: Lymphoma, B-Cell
Issue Date: 2007
Publisher: American Society of Hematology
Publisher version: http://bloodjournal.hematologylibrary.org/content/109/1/271
ISSN: 1528-0020
Citation: Mestre-Escorihuela C, Rubio-Moscardo F, Richter JA, Siebert R, Climent J, Fresquet V, et al. Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas. Blood 2007 ;109(1):271-280.
Abstract
Integrative genomic and gene-expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene-expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them were frequently silenced by epigenetic mechanisms. Notably, the pattern of genetic and epigenetic inactivation differed among B-NHL subtypes. Thus, the P53-inducible PIG7/LITAF was silenced by homozygous deletion in primary mediastinal B-cell lymphoma and by promoter hypermethylation in germinal center lymphoma, the proapoptotic BIM gene presented homozygous deletion in mantle cell lymphoma and promoter hypermethylation in Burkitt lymphoma, the proapoptotic BH3-only NOXA was mutated and preferentially silenced in diffuse large B-cell lymphoma, and INK4c/P18 was silenced by biallelic mutation in mantle-cell lymphoma. Our microarray strategy has identified novel candidate tumor suppressor genes inactivated by genetic and epigenetic mechanisms that substantially vary among the B-NHL subtypes.
Permanent link: http://hdl.handle.net/10171/17897
Appears in Collections:DA - CIMA - Oncología - Síndromes mieloproliferativos - Artículos de Revista
DA - CIMA - Oncología - Oncología molecular - Artículos de Revista
DA - CIMA - Oncología - Terapia celular - Artículos de Revista
DA - CUN - Área de Terapia Celular - Artículos de revista
DA - Medicina - Hematología - Artículos de revista

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