Fusion of dynactin 1 to anaplastic lymphoma kinase in inflammatory myofibroblastic tumor.
Inflammatory myofibroblastic tumor is an uncommon neoplasm that occurs more often in younger patients. Approximately 50% of inflammatory myofibroblastic tumors are characterized by anaplastic lymphoma kinase fusion genes, more commonly TPM3-anaplastic lymphoma kinase and TPM4-anaplastic lymphoma kinase. Herein, we report a novel fusion of dynactin 1 to anaplastic lymphoma kinase in a neck inflammatory myofibroblastic tumor diagnosed in a 7-year-old girl. Histologic evaluation showed a perineurioma-like bland spindle cell neoplasm with positive immunohistochemical staining for anaplastic lymphoma kinase, S-100, and CD34 but negative for epithelial membrane antigen. Standard cytogenetic analysis showed a der(2)t(2;12)(p23;q11). Fluorescence in situ hybridization demonstrated separation of the anaplastic lymphoma kinase locus. 5'-rapid amplification of complementary DNA ends polymerase chain reaction identified an in-frame fusion of dynactin 1 exon 16 on chromosome 2 to anaplastic lymphoma kinase exon 20. Reverse transcription-polymerase chain reaction with specific primers and direct sequencing confirmed the fusion. The structure of the fusion protein retains the cytoskeleton-associated protein-glycine domain and coiled coil domain of dynactin 1 and the receptor tyrosine kinase domain of anaplastic lymphoma kinase. This novel fusion gene is structurally similar to other previously described anaplastic lymphoma kinase fusion genes and may be associated with the unusual morphology and immunophenotype of this tumor.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Xiaoke
X
Wang
Chandra
C
Krishnan
Edward P
EP
Nguyen
Kevin J
KJ
Meyer
Jennifer L
JL
Oliveira
Ping
P
Yang
Eunhee S
ES
Yi
Michele R
MR
Erickson-Johnson
Michael J
MJ
Yaszemski
Avudaiappan
A
Maran
Andre M
AM
Oliveira
D000077548:Anaplastic Lymphoma Kinase; D002648:Child; D002881:Chromosomes, Human, Pair 12; D002889:Chromosomes, Human, Pair 2; D000072159:Dynactin Complex; D005260:Female; D050939:Gene Fusion; D006104:Granuloma, Plasma Cell / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009333:Neck; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014178:Translocation, Genetic
C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D015514:Oncogene Proteins, Fusion; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases