Science · 1994 · 2.4K citations · 19 references
MedicineGeneticsOncologyCancer GeneticsMolecular OncologyOncogenesCancer GenomicsGene Fusions In CancerLymphoid NeoplasmsLymphoid TumorsOncogenic Fusion GenesReceptor Tyrosine Kinase OncogenesAlk Fusion GenesKinase Fusion GenesKinase Fusion OncogenesLymphoid Neoplasm CytogeneticsLymphoma PathogenesisOncogenic Fusion ProteinsSequence SimilarityTyrosine Kinase Receptors
The 2;5 chromosomal translocation, common in anaplastic large‑cell non‑Hodgkin’s lymphomas of activated T cells, produces a hybrid protein linking the NPM nucleolar phosphoprotein to the catalytic domain of ALK. The NPM–ALK fusion gene encodes a truncated kinase expressed in small intestine, testis, and brain but not normal lymphoid cells, and its ectopic activity is implicated in malignant transformation of these lymphomas.
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.
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Major nucleolar proteins shuttle between nucleus and cytoplasm
R.A. Borer, Christian F. Lehner, Hans M. Eppenberger et al. · Cell · 1989 · 1.1K citations