title: Non-muscle myosin heavy chain (MYH9): a new partner fused to ALK in anaplastic large cell lymphoma.
abstract: In anaplastic large cell lymphoma, the ALK gene at 2p23 is known to be fused to NPM, TPM3, TPM4, TFG, ATIC, CLTC, MSN, and ALO17. All of these translocations result in the expression of chimeric ALK transcripts that are translated into fusion proteins with tyrosine kinase activity and oncogenic properties. We report a case showing a restricted cytoplasmic staining pattern of ALK and a novel chromosomal abnormality, t(2;22)(p23;q11.2), demonstrated by fluorescence in situ hybridization analysis. The result of 5' RACE analysis showed that the ALK gene was fused in-frame to a portion of the non-muscle myosin heavy chain gene, MYH9. Nucleotide sequence of the MYH9-ALK chimeric cDNA revealed that the ALK breakpoint was different from all those previously reported. It is localized in the same exonic sequence as MSN-ALK, but 6 bp downstream, resulting in an in-frame fusion of the two partner proteins. In contrast to the previously reported ALK fusion proteins, MYH9-ALK may lack a functional oligomerization domain. However, biochemical analysis showed that the new fusion protein is tyrosine phosphorylated in vivo but seems to lack tyrosine kinase activity in vitro. If further investigations confirm this latter result, the in vivo tyrosine phosphorylation of MYH9-ALK protein could involve mechanisms different from those described in the other ALK hybrid proteins.
authors.affiliation: INSERM U-563, Department of Oncogenesis and Signaling in Hematopoietic Cells, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lamant
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Marie Michèle
authors.initials: MM
authors.lastname: Duplantier
authors.forename: Florence
authors.initials: F
authors.lastname: Armstrong
authors.forename: Ashraf
authors.initials: A
authors.lastname: Raghab
authors.forename: Mukesh
authors.initials: M
authors.lastname: Chhanabhai
authors.forename: Evica
authors.initials: E
authors.lastname: Rajcan-Separovic
authors.forename: Janie
authors.initials: J
authors.lastname: Raghab
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
authors.forename: Estelle
authors.initials: E
authors.lastname: Espinos
mesh_terms: D000595:Amino Acid Sequence; D000077548:Anaplastic Lymphoma Kinase; D001483:Base Sequence; D002648:Child; D005260:Female; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics*; D020409:Molecular Motor Proteins; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D015514:Oncogene Proteins, Fusion; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D018995:Myosin Heavy Chains