Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor.
ALK-positive anaplastic large-cell lymphoma (ALCL) has been recognized as a distinct type of lymphoma in the heterogeneous group of T/Null-ALCL. While most of the ALK-positive ALCL (ALKomas) are characterized by the presence of the NPM-ALK fusion protein, the product of the t(2;5)(p23;q35), 10-20% of ALKomas contain variant ALK fusions, including ATIC-ALK, TFG-ALK, CLTC-ALK (previously designated CLTCL-ALK), TMP3-ALK, and MSN-ALK. TMP3-ALK and TMP4-ALK fusions also have been detected in inflammatory myofibroblastic tumors (IMTs), making clear that aberrations of the ALK gene are not associated exclusively with the pathogenesis of ALK-positive ALCL. Here we report results of molecular studies on two lymphoma cases and one IMT case with variant rearrangements of ALK. 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). These results confirm the recurrent involvement of ALK in IMT and further demonstrate the diversity of ALK fusion partners, with the ability to homodimerize as a common characteristic.
Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, Campus Gasthuisberg O&N 06, Herestraat 49, B-3000 Leuven, Belgium.
Jan
J
Cools
Iwona
I
Wlodarska
Riet
R
Somers
Nicole
N
Mentens
Florence
F
Pedeutour
Brigitte
B
Maes
Christiane
C
De Wolf-Peeters
Patrick
P
Pauwels
Anne
A
Hagemeijer
Peter
P
Marynen
D000005:Abdomen / Q000473:pathology; D000251:Adenosine Triphosphatases; D000293:Adolescent; D000595:Amino Acid Sequence / Q000235:genetics; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics*; D000077548:Anaplastic Lymphoma Kinase; D001483:Base Sequence / Q000235:genetics; D003001:Cloning, Molecular / Q000379:methods; D005260:Female; D006104:Granuloma, Plasma Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008161:Lumbosacral Region / Q000473:pathology; D017728:Lymphoma, Large-Cell, Anaplastic / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
D015514:Oncogene Proteins, Fusion; D011506:Proteins; C408996:oncoprotein CLTCL-ALK; C557998:RNF213 protein, human; D044767:Ubiquitin-Protein Ligases; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D000251:Adenosine Triphosphatases; D000604:Amino Acyl-tRNA Synthetases; C019975:cysteinyl-tRNA synthetase