Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.
The 2;5 chromosomal translocation occurs in most anaplastic large-cell non-Hodgkin's lymphomas arising from activated T lymphocytes. This rearrangement was shown to fuse the NPM nucleolar phosphoprotein gene on chromosome 5q35 to a previously unidentified protein tyrosine kinase gene, ALK, on chromosome 2p23. In the predicted hybrid protein, the amino terminus of nucleophosmin (NPM) is linked to the catalytic domain of anaplastic lymphoma kinase (ALK). Expressed in the small intestine, testis, and brain but not in normal lymphoid cells, ALK shows greatest sequence similarity to the insulin receptor subfamily of kinases. Unscheduled expression of the truncated ALK may contribute to malignant transformation in these lymphomas.
Morris
S W
SW
Department of Experimental Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Kirstein
M N
MN
Valentine
M B
MB
Dittmer
K G
KG
Shapiro
D N
DN
Saltman
D L
DL
Look
A T
AT
D000595:Amino Acid Sequence; D000077548:Anaplastic Lymphoma Kinase; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D002471:Cell Transformation, Neoplastic; D016386:Chromosome Walking; D002889:Chromosomes, Human, Pair 2; D002895:Chromosomes, Human, Pair 5; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007421:Intestine, Small / Q000201:enzymology; D017728:Lymphoma, Large-Cell, Anaplastic / Q000737:chemistry / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D000090243:Nucleophosmin; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D016415:Sequence Alignment; D015398:Signal Transduction; D013737:Testis / Q000201:enzymology; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D000090243:Nucleophosmin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases