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: Magda Pinyol, Silvia Bea, Laura Plà, Vincent Ribrag, Jacques Bosq, Andreas Rosenwald, Elias Campo, Pedro Jares
• Journal: Blood (Blood) Vol. 109 Issue 12 Pg. 5422-9 (Jun 15 2007) ISSN: 0006-4971 [Print] United States
• PMID: 17332242 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon, Nonsense
• Dental Enamel Proteins
• Protein Isoforms
• RNA, Messenger
• Retinoblastoma Protein
• Tumor Suppressor Protein p53
• leucine-rich amelogenin peptide

Topics

• Algorithms
• Cell Line, Tumor
• Codon, Nonsense
• Dental Enamel Proteins (genetics)
• Gene Expression Profiling
• Gene Silencing
• Humans
• Lymphoma, Mantle-Cell (genetics)
• Microarray Analysis
• Protein Isoforms
• RNA, Messenger (metabolism)
• Retinoblastoma Protein (genetics)
• Tumor Suppressor Protein p53 (genetics)