PMID- 10216106
OWN - NLM
STAT- MEDLINE
DCOM- 19990518
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 93
IP  - 9
DP  - 1999 May 1
TI  - A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a
      (1;2)(q25;p23) translocation.
PG  - 3088-95
AB  - Anaplastic large cell lymphomas (ALCL) are frequently associated with the
      t(2;5)(p23;q35). This translocation fuses the nucleophosmin (NPM) gene at 5q35,
      which encodes a nucleolar protein involved in shuttling ribonucleoproteins from
      the cytoplasm to the nucleus, to the anaplastic lymphoma kinase (ALK) gene at
      2p23, encoding a tyrosine kinase receptor. In this report, we describe a typical 
      case of ALCL whose malignant cells exhibited a novel (1;2)(q25;p23)
      translocation. These cells expressed ALK protein, but, in contrast to
      t(2;5)-positive ALCL (which show cytoplasmic, nuclear, and nucleolar staining),
      labeling was restricted to the malignant cell cytoplasm. Using a polymerase chain
      reaction (PCR)-based technique to walk on chromosome 2 from the known ALK gene
      across the breakpoint, we showed that the gene involved at 1q25 is TPM3, encoding
      a nonmuscular tropomyosin. We subsequently identified, using reverse
      transcription-PCR analysis of cases showing similar ALK cytoplasm-restricted
      staining, fusion of the ALK and TPM3 genes in 2 other cases of ALCL. The TPM3
      gene has been previously found in papillary thyroid carcinomas as a fusion
      partner with the TRK kinase gene. We showed that TPM3 is constitutively expressed
      in lymphoid cell lines, suggesting that, in these t(1;2)-bearing ALCL cases, the 
      TPM3 gene contributes an active promoter for ALK expression. Activation of the
      ALK catalytic domain probably results from homodimerization of the hybrid protein
      TPM3-ALK, through the TPM3 protein-protein interaction domain. The present cases 
      of ALCL associated with a novel t(1;2)(q25;p23) demonstrate that at least one
      fusion partner other than NPM can activate the intracytoplasmic domain of the ALK
      kinase.
FAU - Lamant, L
AU  - Lamant L
AD  - Department of Pathology, Hematology Laboratory, and UPCM-ERS 1590 CNRS, CHU
      Purpan, Toulouse, France.
FAU - Dastugue, N
AU  - Dastugue N
FAU - Pulford, K
AU  - Pulford K
FAU - Delsol, G
AU  - Delsol G
FAU - Mariame, B
AU  - Mariame B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA Primers)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Tropomyosin)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Anaplastic Lymphoma Kinase
MH  - Base Sequence
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 1
MH  - *Chromosomes, Human, Pair 2
MH  - DNA Primers
MH  - Humans
MH  - Karyotyping
MH  - Lymphoma, Large-Cell, Anaplastic/*genetics/pathology
MH  - Molecular Sequence Data
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Protein-Tyrosine Kinases/*genetics
MH  - Receptor Protein-Tyrosine Kinases
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Translocation, Genetic
MH  - Tropomyosin/*genetics
EDAT- 1999/04/27 00:00
MHDA- 1999/04/27 00:01
CRDT- 1999/04/27 00:00
PHST- 1999/04/27 00:00 [pubmed]
PHST- 1999/04/27 00:01 [medline]
PHST- 1999/04/27 00:00 [entrez]
AID - S0006-4971(20)59632-8 [pii]
PST - ppublish
SO  - Blood. 1999 May 1;93(9):3088-95.