RANBP2 and CLTC are involved in ALK rearrangements in inflammatory myofibroblastic tumors.
Inflammatory myofibroblastic tumors (IMTs) are rare soft tissue tumors occurring primarily in children and young adults. ALK gene rearrangements have been identified in this neoplasm, with fusion of the ALK gene at 2p23 to a number of different partner genes. Metaphase cytogenetic analyses of these tumors have been relatively few, however, and may help to identify additional variant partners. We report on an IMT from a 2-year-old boy with a karyotype of 45,XY,der(2)inv(2)(p23q12)del(2)(p11.1p11.2),-22. FISH showed ALK-RANBP2 fusion in this tumor. The breakpoint was cloned and the fusion was confirmed, making this the third reported case of IMT with ALK-RANBP2 fusion. In addition, we identified the ALK fusion partner in a previously reported IMT with t(2;17)(p23;q23) as CLTC, a gene reported to be involved in four other IMTs, and showed that the breakpoint involved a novel ALK-CLTC fusion. FISH evaluation of nine other IMTs identified CLTC as the fusion partner in one additional case, but RANBP2 was not involved in the remaining eight IMTs, suggesting that the variant partners involved in ALK rearrangements in IMTs are diverse.
Patel
Ankita S
AS
Department of Pathology, Johns Hopkins University, Park SB-202, 600 N. Wolfe Street, Baltimore MD 21287, USA.
Murphy
Kathleen M
KM
Hawkins
Anita L
AL
Cohen
Julie S
JS
Long
Patricia P
PP
Perlman
Elizabeth J
EJ
Griffin
Constance A
CA
D000077548:Anaplastic Lymphoma Kinase; D001483:Base Sequence; D002675:Child, Preschool; D007446:Chromosome Inversion; D033922:Clathrin Heavy Chains / Q000235:genetics / Q000502:physiology*; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007621:Karyotyping; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000502:physiology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases; D012983:Soft Tissue Neoplasms / Q000235:genetics*
C529682:ALK-RANBP2 fusion protein, human; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; C094493:ran-binding protein 2; D033922:Clathrin Heavy Chains; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases