PMID- 16051735
OWN - NLM
STAT- MEDLINE
DCOM- 20051130
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 106
IP  - 9
DP  - 2005 Nov 1
TI  - Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and 
      TRAIL-R2 as candidate dosage-dependent tumor suppressor genes.
PG  - 3214-22
AB  - Deletions of chromosome 8p are a recurrent event in B-cell non-Hodgkin lymphoma 
      (B-NHL), suggesting the presence of a tumor suppressor gene. We have 
      characterized these deletions using comparative genomic hybridization to 
      microarrays, fluorescence in situ hybridization (FISH) mapping, DNA sequencing, 
      and functional studies. A minimal deleted region (MDR) of 600 kb was defined in 
      chromosome 8p21.3, with one mantle cell lymphoma cell line (Z138) exhibiting 
      monoallelic deletion of 650 kb. The MDR extended from bacterial artificial 
      chromosome (BAC) clones RP11-382J24 and RP11-109B10 and included the tumor 
      necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene loci. 
      Sequence analysis of the individual expressed genes within the MDR and DNA 
      sequencing of the entire MDR in Z138 did not reveal any mutation. Gene expression 
      analysis and quantitative reverse transcriptase-polymerase chain reaction 
      (QRT-PCR) showed down-regulation of TRAIL-R1 and TRAIL-R2 receptor genes as a 
      consistent event in B-NHL with 8p21.3 loss. Epigenetic inactivation was excluded 
      via promoter methylation analysis. In vitro studies showed that TRAIL-induced 
      apoptosis was dependent on TRAIL-R1 and/or -R2 dosage in most tumors. Resistance 
      to apoptosis of cell lines with 8p21.3 deletion was reversed by restoration of 
      TRAIL-R1 or TRAIL-R2 expression by gene transfection. Our data suggest that 
      TRAIL-R1 and TRAIL-R2 act as dosage-dependent tumor suppressor genes whose 
      monoallelic deletion can impair TRAIL-induced apoptosis in B-cell lymphoma.
FAU - Rubio-Moscardo, Fanny
AU  - Rubio-Moscardo F
AD  - Center for Applied Medical Research (CIMA), Division of Oncology, University of 
      Navarra, Avda Pio XII, 55, Pamplona 31008, Spain.
FAU - Blesa, David
AU  - Blesa D
FAU - Mestre, Cinta
AU  - Mestre C
FAU - Siebert, Reiner
AU  - Siebert R
FAU - Balasas, Theo
AU  - Balasas T
FAU - Benito, Adalberto
AU  - Benito A
FAU - Rosenwald, Andreas
AU  - Rosenwald A
FAU - Climent, Joan
AU  - Climent J
FAU - Martinez, Jose I
AU  - Martinez JI
FAU - Schilhabel, Markus
AU  - Schilhabel M
FAU - Karran, E Lorraine
AU  - Karran EL
FAU - Gesk, Stefan
AU  - Gesk S
FAU - Esteller, Manel
AU  - Esteller M
FAU - deLeeuw, Ronald
AU  - deLeeuw R
FAU - Staudt, Louis M
AU  - Staudt LM
FAU - Fernandez-Luna, Jose Luis
AU  - Fernandez-Luna JL
FAU - Pinkel, Daniel
AU  - Pinkel D
FAU - Dyer, Martin J S
AU  - Dyer MJ
FAU - Martinez-Climent, Jose A
AU  - Martinez-Climent JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050728
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFRSF10A protein, human)
RN  - 0 (TNFRSF10B protein, human)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Apoptosis
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Cell Line, Tumor
MH  - *Chromosome Deletion
MH  - Chromosomes, Human, Pair 8/*genetics
MH  - Down-Regulation
MH  - Gene Expression Profiling
MH  - Genes, Tumor Suppressor/*physiology
MH  - Humans
MH  - Lymphoma, B-Cell/*genetics
MH  - Membrane Glycoproteins/metabolism
MH  - Mutation/genetics
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand
MH  - Receptors, Tumor Necrosis Factor/*genetics/metabolism
MH  - TNF-Related Apoptosis-Inducing Ligand
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Tumor Suppressor Proteins/*genetics/metabolism
EDAT- 2005/07/30 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/07/30 09:00
PHST- 2005/07/30 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/07/30 09:00 [entrez]
AID - S0006-4971(20)68571-8 [pii]
AID - 10.1182/blood-2005-05-2013 [doi]
PST - ppublish
SO  - Blood. 2005 Nov 1;106(9):3214-22. doi: 10.1182/blood-2005-05-2013. Epub 2005 Jul 
      28.