Molecular characterization of a new ALK translocation involving moesin (MSN-ALK) in anaplastic large cell lymphoma

The majority of anaplastic large cell lymphomas (ALCL) are associated with chromosomal abnormalities affecting the anaplastic lymphoma kinase (ALK) ge ne which result in the expression of hybrid AFK fusion proteins in the tumo r cells. In most of these tumors, the hybrid gene comprises the 5' region o f nucleophosmin (NPM) fused in frame to the 3' portion of ALK, resulting in the expression of the chimeric oncogenic tyrosine kinase NPM-ALK. However, other variant rearrangements have been described in which ALK fuses to a p artner other than NPM. Here we have identified the moesin (MSN) gene at Xq1 1-12 as a new partner of ALK in a case of ALCL which exhibited a distinctiv e membrane-restricted pattern of ALK labeling. The hybrid MSN-ALK protein h ad a molecular weight of 125 kd and contained an active tyrosine kinase dom ain. The unique membrane staining pattern of ALK is presumed to reflect ass ociation of moesin with cell membrane proteins. In contrast to other transl ocations involving the ALK gene, the ALK breakpoint in this case occurred w ithin the exonic sequence coding for the juxtamembrane portion of ALK. Iden tification of the genomic breakpoint confirmed the in-frame fusion of the w hole MSN intron 10 to a 17 bp shorter juxtamembrane exon of ALK. The breakp oint in der(2) chromosome showed a deletion, including 30 bp of ALK and 36 bp of MSN genes. These findings indicate that MSN may act as an alternative fusion partner for activation of ALK in ALCL and provide further evidence that oncogenic activation of ALK may occur at different intracellular locat ions.