title: Inactivation of RB1 in mantle-cell lymphoma detected by nonsense-mediated mRNA decay pathway inhibition and microarray analysis.
abstract: Mantle-cell lymphoma (MCL) is genetically characterized by the translocation t(11;14)(q13;q32) and a high number of secondary chromosomal abnormalities. To identify genes inactivated in this lymphoma, we examined 5 MCL cell lines following a strategy previously described in tumors with microsatellite instability that is based on the combined inhibition of the nonsense-mediated mRNA decay pathway and gene-expression profiling. This approach, together with the design of a conservative algorithm for analysis of the results, allowed the identification of 3 genes carrying premature stop codons. These genes were p53 with a mutation previously described in JEKO-1, the leukocyte-derived arginine aminopeptidase (LRAP) gene in REC-1 that showed a new splicing isoform generating a premature stop codon, and RB1 in UPN-1 that contained an intragenic homozygous deletion resulting in a truncated transcript and total loss of protein expression. The new LRAP isoform was detected also in 2 primary MCLs, whereas inactivating intragenic deletions of RB1 were found in the primary tumor from which UPN-1 was derived and 1 additional blastoid MCL. These tumors carried a concomitant inactivation of p53, whereas p16INK4a was wild type. These results indicate for the first time that RB1 may be inactivated in aggressive MCL by intragenic deletions.
authors.affiliation: Genomics Unit, Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Magda
authors.initials: M
authors.lastname: Pinyol
authors.forename: Silvia
authors.initials: S
authors.lastname: Bea
authors.forename: Laura
authors.initials: L
authors.lastname: Plà
authors.forename: Vincent
authors.initials: V
authors.lastname: Ribrag
authors.forename: Jacques
authors.initials: J
authors.lastname: Bosq
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Pedro
authors.initials: P
authors.lastname: Jares
mesh_terms: D000465:Algorithms; D045744:Cell Line, Tumor; D018389:Codon, Nonsense; D003746:Dental Enamel Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000235:genetics*; D046228:Microarray Analysis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D003746:Dental Enamel Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C067432:leucine-rich amelogenin peptide