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Non‐muscle myosin heavy chain (MYH9): A new partner fused to ALK in anaplastic large cell lymphoma
Author(s) -
Lamant Laurence,
Gascoyne Randy D.,
Duplantier Marie Michèle,
Armstrong Florence,
Raghab Ashraf,
Chhanabhai Mukesh,
RajcanSeparovic Evica,
Raghab Janie,
Delsol Georges,
Espinos Estelle
Publication year - 2003
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.10232
Subject(s) - anaplastic lymphoma kinase , microbiology and biotechnology , fusion protein , fusion gene , biology , anaplastic large cell lymphoma , complementary dna , fluorescence in situ hybridization , tyrosine , gene , chemistry , biochemistry , lymphoma , recombinant dna , chromosome , medicine , malignant pleural effusion , immunology , surgery , pleural effusion
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. © 2003 Wiley‐Liss, Inc.