With the exception of ALK-positive anaplastic large cell lymphoma (ALCL), which is defined on the basis of ALK rearrangements, genetic features play little role in the definition of other disease entities.
Genetic alterations of ALK are associated with a number of cancers, including anaplastic large cell lymphoma (ALCL) and a subset of non-small cell lung cancer (NSCLC).
The expression of CD30 and ALK1 with ALK gene rearrangement raised the possibility of three diagnoses: a primary cutaneous anaplastic large cell lymphoma (ALCL), a cutaneous inflammatory myofibroblastic tumor (IMT), an AFH of the skin associated with ALK gene rearrangement and CD30 positivity.
Methotrexate significantly induced apoptosis in ALK inhibitor-resistant cells expressing the NPM-ALK mutant harboring the point mutation, G262R, and in ALCL patient-derived NPM-ALK-positive Ki-JK cells.
CLTC encodes a major subunit of clathrin, a multimeric protein on cytoplasmic organelles, and is a known recurrent fusion partner of the ALK tyrosine kinase gene in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumors.
The majority of ALCL carries the translocation t(2;5) that encodes for the oncogenic tyrosine kinase NPM-ALK, fundamental for survival, proliferation, and migration of transformed T cells.
These findings represent the first recurrent translocation reported in ALK-negative ALCL and highlight the utility of massively parallel genomic sequencing to discover novel translocations in lymphoma and other cancers.
Our study led to the detection of the CLTC-ALK fusion in an ALCL case and to the identification of two novel fusion partners of ALK: ALO17 (KIAA1618), a gene with unknown function, which was fused to ALK in an ALCL case with a t(2;17)(p23;q25), and CARS, encoding the cysteinyl-tRNA synthetase, which was fused to ALK in an IMT case with a t(2;11;2)(p23;p15;q31).
The anaplastic lymphoma kinase (ALK) gene was initially identified as a fusion partner of the nucleophosmin gene in anaplastic large-cell lymphoma with t(2;5)(p23;q35) translocation, and then described with different genetic abnormalities in a number of tumors.
To evaluate this entity in a pediatric population, 36 cases of childhood large cell lymphoma were evaluated for abnormalities of the anaplastic lymphoma kinase (ALK) gene that has been associated with ALCL morphology and immunophenotype.
The ALK (anaplastic lymphoma kinase) RTK was originally identified as a member of the insulin receptor subfamily of RTKs that acquires transforming capability when truncated and fused to NPM (nucleophosmin) in the t(2;5) chromosomal rearrangement associated with ALCL (anaplastic large cell lymphoma).
Fluorescence in situ hybridization (FISH) showed rearrangement of the ALK gene, which usually results from the t(2;5) translocation, present in most anaplastic large cell lymphomas.
TYK2 is a member of the JAK family of tyrosine kinases that is involved in chromosomal translocation-induced fusion proteins found in anaplastic large cell lymphomas (ALCL) that lack rearrangements activating the anaplastic lymphoma kinase (ALK).
Since the identification of the ALK gene in 1994 as the target of the t(2;5) chromosomal translocation in anaplastic large cell lymphoma, ALK has been proven a remarkably promiscuous oncogene.
The discovery of the t(2;5), involving the anaplastic lymphoma kinase (ALK) gene on chromosome 2 and the nucleophosmin (NPM) gene on chromosome 5 in the majority of systemic ALCL, has soon pointed out that ALCL is a clinically and biologically heterogeneous disease.
We have developed a PCT methodology which has enabled the detection of the NPM-ALK rearrangements amongst seven t(2;5)(p23;q35)ALCL cases based on a long-range PCR of genomic DNA.
The anaplastic lymphoma kinase (ALK) is chromosomally rearranged in a subset of certain cancers, including 2% to 7% of non-small cell lung cancers (NSCLC) and ∼70% of anaplastic large cell lymphomas (ALCL).
Parallel quantification of <i>NPM-ALK</i> transcripts and fusion genes in ALCL cell lines treated with the ALK kinase inhibitor crizotinib illustrates the potential value of supplementary DNA-based quantification in particular clinical settings.
Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL) cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients.
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.
The t(2;5)(p23;q35) translocation, associated with anaplastic large-cell lymphoma (ALCL), results in the production of the nucleolar protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) protein.