Document Detail


Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas.
MedLine Citation:
PMID:  16960149     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Cinta Mestre-Escorihuela; Fanny Rubio-Moscardo; Jose A Richter; Reiner Siebert; Joan Climent; Vicente Fresquet; Elena Beltran; Xabier Agirre; Isabel Marugan; Miguel Marín; Andreas Rosenwald; Kei-Ji Sugimoto; Luise M Wheat; E Loraine Karran; Juan F García; Lydia Sanchez; Felipe Prosper; Louis M Staudt; Daniel Pinkel; Martin J S Dyer; Jose A Martinez-Climent
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-09-07
Journal Detail:
Title:  Blood     Volume:  109     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-27     Completed Date:  2007-02-20     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  271-80     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / genetics
Apoptosis Regulatory Proteins / genetics*
Biopsy
Carrier Proteins / genetics*
Cell Line, Tumor
Chromosome Mapping
Chromosomes, Human / genetics,  ultrastructure
Cyclin-Dependent Kinase Inhibitor p18 / genetics*
DNA Methylation
DNA Mutational Analysis
DNA, Neoplasm / genetics
Epigenesis, Genetic
Gene Dosage
Gene Expression Regulation, Neoplastic
Gene Silencing
Genes, Tumor Suppressor*
Homeodomain Proteins / genetics*
Homozygote
Humans
Lymphoma, B-Cell / classification,  genetics*,  immunology,  pathology
Membrane Proteins / genetics*
Nuclear Proteins / genetics*
Nucleic Acid Hybridization
Oligonucleotide Array Sequence Analysis
Point Mutation
Promoter Regions, Genetic / genetics
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins c-bcl-2 / genetics*
Sequence Deletion*
Sorting Nexins
Transcription Factors / genetics*
Vesicular Transport Proteins / genetics*
Grant Support
ID/Acronym/Agency:
MC_U132670597//Medical Research Council
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/CDKN2C protein, human; 0/Carrier Proteins; 0/Cyclin-Dependent Kinase Inhibitor p18; 0/DNA, Neoplasm; 0/Homeodomain Proteins; 0/LITAF protein, human; 0/Membrane Proteins; 0/Nuclear Proteins; 0/PMAIP1 protein, human; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/SNX25 protein, human; 0/SORBS2 protein, human; 0/Sorting Nexins; 0/Transcription Factors; 0/Vesicular Transport Proteins

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