PMID- 12560219
OWN - NLM
STAT- MEDLINE
DCOM- 20030711
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 101
IP  - 11
DP  - 2003 Jun 1
TI  - MALT1 is deregulated by both chromosomal translocation and amplification in 
      B-cell non-Hodgkin lymphoma.
PG  - 4539-46
AB  - The MALT1 gene was identified through its involvement in t(11;18)(q21;q21), seen 
      in 30% of cases of mucosa-associated lymphoid tissue (MALT) lymphoma. Here, we 
      show that deregulated MALT1 expression may occur in B-cell non-Hodgkin lymphoma 
      (B-NHL) of various histologic subtypes either through translocation to the 
      immunoglobulin heavy chain (IGH) locus or by genomic amplification. First, 2 
      cases, one case of MALT lymphoma and another of aggressive marginal zone lymphoma 
      (MZL) with t(14;18)(q32;q21), cytogenetically identical to the translocation 
      involving BCL2, were shown by fluorescence in situ hybridization (FISH) to 
      involve MALT1, which lies about 5 Mb centromeric of BCL2. Molecular cloning of 
      both by long-distance inverse polymerase chain reaction showed breakpoints lying 
      1 to 2 kilobase (kb) centromeric of the first 5' MALT1 exon; both cases showed 
      MALT1 overexpression at either RNA or protein levels. Second, we examined the 
      structure and gene expression profile of genomic amplifications involving 18q21 
      in a panel of 40 B-NHL cell lines using comparative genomic hybridization to 
      microarrays (array CGH) and gene expression profiling techniques. Using array 
      CGH, 2 peaks of genomic amplification were observed, one centered around BCL2 and 
      the other around MALT1. Ofthe 3 cell lines with MALT1 amplification, 2 showed 
      MALT1 overexpression as assessed by gene profiling, quantitative reverse 
      transcription-polymerase chain reaction (QRT-PCR), and Western blotting. To 
      determine if comparable events occurred in primary MALT and splenic MZL tumors, 
      40 cases were analyzed by FISH or QRT-PCR; genomic amplification and MALT1 
      overexpression were seen in 2 cases. Together, these data implicate MALT1 as a 
      dominant oncogene that may play a role in the pathogenesis of B-NHL.
FAU - Sanchez-Izquierdo, Dolors
AU  - Sanchez-Izquierdo D
AD  - Department of Hematology and Medical Oncology, Hospital Clinico, University of 
      Valencia, Spain.
FAU - Buchonnet, Gerard
AU  - Buchonnet G
FAU - Siebert, Reiner
AU  - Siebert R
FAU - Gascoyne, Randy D
AU  - Gascoyne RD
FAU - Climent, Joan
AU  - Climent J
FAU - Karran, Loraine
AU  - Karran L
FAU - Marin, Miguel
AU  - Marin M
FAU - Blesa, David
AU  - Blesa D
FAU - Horsman, Douglas
AU  - Horsman D
FAU - Rosenwald, Andreas
AU  - Rosenwald A
FAU - Staudt, Louis M
AU  - Staudt LM
FAU - Albertson, Donna G
AU  - Albertson DG
FAU - Du, Ming-Qing
AU  - Du MQ
FAU - Ye, Hongtao
AU  - Ye H
FAU - Marynen, Peter
AU  - Marynen P
FAU - Garcia-Conde, Javier
AU  - Garcia-Conde J
FAU - Pinkel, Daniel
AU  - Pinkel D
FAU - Dyer, Martin J S
AU  - Dyer MJ
FAU - Martinez-Climent, Jose Angel
AU  - Martinez-Climent JA
LA  - eng
GR  - U01-CA84967-1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030130
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Neoplasm)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.22.- (MALT1 protein, human)
RN  - EC 3.4.22.- (Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein)
SB  - IM
MH  - Aged
MH  - Caspases
MH  - Chromosomes, Human, Pair 14
MH  - Chromosomes, Human, Pair 18
MH  - Female
MH  - *Gene Amplification
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, bcl-2
MH  - Humans
MH  - Lymphoma, B-Cell/etiology/*genetics/pathology
MH  - Lymphoma, B-Cell, Marginal Zone/etiology/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
MH  - Neoplasm Proteins/biosynthesis/*genetics
MH  - RNA, Neoplasm/analysis
MH  - *Translocation, Genetic
EDAT- 2003/02/01 04:00
MHDA- 2003/07/12 05:00
CRDT- 2003/02/01 04:00
PHST- 2003/02/01 04:00 [pubmed]
PHST- 2003/07/12 05:00 [medline]
PHST- 2003/02/01 04:00 [entrez]
AID - S0006-4971(20)54085-8 [pii]
AID - 10.1182/blood-2002-10-3236 [doi]
PST - ppublish
SO  - Blood. 2003 Jun 1;101(11):4539-46. doi: 10.1182/blood-2002-10-3236. Epub 2003 Jan 
      30.