PMID- 9763551
OWN - NLM
STAT- MEDLINE
DCOM- 19981109
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 92
IP  - 8
DP  - 1998 Oct 15
TI  - The cryptic inv(2)(p23q35) defines a new molecular genetic subtype of 
      ALK-positive anaplastic large-cell lymphoma.
PG  - 2688-95
AB  - Recently, a distinctive entity characterized by expression of the anaplastic 
      lymphoma kinase (ALK) protein [most frequently due to the 
      t(2;5)(p23;q35)-associated NPM-ALK fusion] has emerged within the heterogenous 
      group of non-Hodgkin's lymphomas (NHL) classified as anaplastic large-cell 
      lymphoma (ALCL). Sporadic variant 2p23/ALK abnormalities identified in 
      ALK-positive ALCL indicate that genes other than NPM may also be involved in the 
      deregulation of ALK and lymphomagenesis. We report here three cases with an 
      inv(2)(p23q35) detected by fluorescence in situ hybridization (FISH) in young 
      male patients with ALK-positive ALCL. In contrast to ALCL cases with the 
      classical t(2;5)(p23;q35) that usually show both cytoplasmic and nuclear or 
      predominantly nuclear alone localization of the NPM-ALK chimeric product, in all 
      three cases with an inv(2)(p23q35) the ALK protein accumulated in the cytoplasm 
      only, supporting the previous assumption that the oncogenic potential of ALK may 
      not be dependent on its nuclear localization. As the first step to identify the 
      ALK partner gene involved in the inv(2)(p23q35), we performed extensive FISH 
      studies and demonstrated that the 2q35 breakpoint occurred within the 1,750-kb 
      region contained within the 914E7 YAC. Moreover, a striking association of the 
      inv(2)(p23q35) with a secondary chromosomal change, viz, 
      ider(2)(q10)inv(2)(p23q35), carrying two additional copies of the putative 
      ALK-related fusion gene, was found in all three patients, suggesting that, in 
      contrast to the standard t(2;5)/NPM-ALK fusion, multiple copies of the putative 
      2q35-ALK chimeric gene may be required for efficient tumor development. In 
      summary, we demonstrate that the inv(2)(p23q35), a variant of the 
      t(2;5)(p23;q35), is a recurrent chromosomal abnormality in ALK-positive ALCL, the 
      further characterization of which should provide new insight into the 
      pathogenesis of these lymphomas.
CI  - Copyright 1998 by The American Society of Hematology.
FAU - Wlodarska, I
AU  - Wlodarska I
AD  - Center for Human Genetics, Department of Pathology, Hematology, K.U. Leuven, 
      Leuven, Belgium.
FAU - De Wolf-Peeters, C
AU  - De Wolf-Peeters C
FAU - Falini, B
AU  - Falini B
FAU - Verhoef, G
AU  - Verhoef G
FAU - Morris, S W
AU  - Morris SW
FAU - Hagemeijer, A
AU  - Hagemeijer A
FAU - Van den Berghe, H
AU  - Van den Berghe H
LA  - eng
GR  - CA 21765/CA/NCI NIH HHS/United States
GR  - CA 69129/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.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
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  - Adult
MH  - Anaplastic Lymphoma Kinase
MH  - *Chromosome Inversion
MH  - Chromosomes, Human, Pair 2/genetics/*ultrastructure
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Lymphoma, Large-Cell, Anaplastic/*classification/genetics/pathology
MH  - Male
MH  - Protein-Tyrosine Kinases/*genetics
MH  - Proto-Oncogenes
MH  - Receptor Protein-Tyrosine Kinases
EDAT- 1998/10/09 00:00
MHDA- 1998/10/09 00:01
CRDT- 1998/10/09 00:00
PHST- 1998/10/09 00:00 [pubmed]
PHST- 1998/10/09 00:01 [medline]
PHST- 1998/10/09 00:00 [entrez]
AID - S0006-4971(20)76186-0 [pii]
PST - ppublish
SO  - Blood. 1998 Oct 15;92(8):2688-95.