TY - JOUR
T1 - TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors
AU - Lawrence, Brandon
AU - Perez-Atayde, Antonio
AU - Hibbard, Michele K.
AU - Rubin, Brian P.
AU - Cin, Paola Dal
AU - Pinkus, Jack L.
AU - Pinkus, Geraldine S.
AU - Xiao, Sheng
AU - Yi, Eunhee S.
AU - Fletcher, Christopher D.M.
AU - Fletcher, Jonathan A.
PY - 2000/8
Y1 - 2000/8
N2 - Inflammatory myofibroblastic tumors (IMTs) are neoplastic mesenchymal proliferations featuring an inflammatory infiltrate composed primarily of lymphocytes and plasma cells. The myofibroblastic cells in some IMTs contain chromosomal rearrangements involving the ALK receptor tyrosine-kinase locus region (chromosome band 2p23). ALK - which is normally restricted in its expression to neural tissues - is expressed strikingly in the IMT cells with 2p23 rearrangements. We now report a recurrent oncogenic mechanism, in IMTs, in which tropomyosin (TPM) N-terminal coiled-coil domains are fused to the ALK C-terminal kinase domain. We have cloned two ALK fusion genes, TPM4-ALK and TPM3-ALK, which encode ˜95-kd fusion oncoproteins characterized by constitutive kinase activity and tyrosylphosphorylation. Immunohistochemical and molecular correlations, in other IMTs, implicate non-TPM ALK oncoproteins that are predominantly cytoplasmic or predominantly nuclear, presumably depending on the subcellular localization of the ALK fusion partner. Notably, a TPM3-ALK oncogene was reported recently in anaplastic lymphoma, and TPM3-ALK is thereby the first known fusion oncogene that transforms, in vivo, both mesenchymal and lymphoid human cell lineages.
AB - Inflammatory myofibroblastic tumors (IMTs) are neoplastic mesenchymal proliferations featuring an inflammatory infiltrate composed primarily of lymphocytes and plasma cells. The myofibroblastic cells in some IMTs contain chromosomal rearrangements involving the ALK receptor tyrosine-kinase locus region (chromosome band 2p23). ALK - which is normally restricted in its expression to neural tissues - is expressed strikingly in the IMT cells with 2p23 rearrangements. We now report a recurrent oncogenic mechanism, in IMTs, in which tropomyosin (TPM) N-terminal coiled-coil domains are fused to the ALK C-terminal kinase domain. We have cloned two ALK fusion genes, TPM4-ALK and TPM3-ALK, which encode ˜95-kd fusion oncoproteins characterized by constitutive kinase activity and tyrosylphosphorylation. Immunohistochemical and molecular correlations, in other IMTs, implicate non-TPM ALK oncoproteins that are predominantly cytoplasmic or predominantly nuclear, presumably depending on the subcellular localization of the ALK fusion partner. Notably, a TPM3-ALK oncogene was reported recently in anaplastic lymphoma, and TPM3-ALK is thereby the first known fusion oncogene that transforms, in vivo, both mesenchymal and lymphoid human cell lineages.
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U2 - 10.1016/S0002-9440(10)64550-6
DO - 10.1016/S0002-9440(10)64550-6
M3 - Article
C2 - 10934142
AN - SCOPUS:0033890820
SN - 0002-9440
VL - 157
SP - 377
EP - 384
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
M1 - 64550
ER -