Fusion of the <i>SEC31L1</i> and <i>ALK</i> genes in an inflammatory myofibroblastic tumor

<jats:title>Abstract</jats:title><jats:p>Inflammatory myofibroblastic tumor (IMT) is a neoplasm composed of myofibroblastic spindle cells and infiltrating inflammatory cells. Cytogenetic analyses have revealed that a subgroup of IMT, in particular among children and young adults, harbors clonal chromosomal rearrangements involving chromosome band 2p23. Further, molecular genetic studies have shown that these rearrangements target the <jats:italic>ALK</jats:italic> gene, serving as the 3′‐partner in fusion genes with various translocation partners. In the present study, we describe the finding of a novel <jats:italic>SEC31L1/ALK</jats:italic> fusion gene in an intraabdominal IMT of a young man. G‐band analysis revealed a translocation t(2;4)(p23;q21) and subsequent fluorescence <jats:italic>in situ</jats:italic> hybridization with locus‐specific probes strongly indicated disruption of the <jats:italic>ALK</jats:italic> locus on chromosome 2. Immunostaining with monoclonal mouse anti‐human CD246 ALK Protein showed diffuse cytoplasmic positivity. Using reverse primers for the <jats:italic>ALK‐</jats:italic>gene, we could, by 5′‐RACE methodology, amplify a single 1.2 kb fragment. Sequence analysis showed that the fragment was a hybrid cDNA product in which nt 3012 of <jats:italic>SEC31L1</jats:italic> (NM_016211), located in band 4q21, was fused in‐frame to nt 4080 of <jats:italic>ALK</jats:italic> (NM_004304). RT‐PCR with two sets of primer pairs specific for <jats:italic>SEC31L1</jats:italic> and <jats:italic>ALK</jats:italic> amplified two transcripts, which at sequencing corresponded to two types of chimeric <jats:italic>SEC31L1/ALK</jats:italic> transcripts. In the long, type I, transcript nt 3012 of <jats:italic>SEC31L1</jats:italic> (NM_016211) was fused in‐frame to nt 4080 of <jats:italic>ALK</jats:italic>. In the short, type II, transcript nt 2670 of <jats:italic>SEC31L1</jats:italic> was fused in‐frame to nt 4080 of <jats:italic>ALK</jats:italic>. Genomic PCR and subsequent sequencing showed that the breakpoints were located in intron 23 of <jats:italic>SEC31L1</jats:italic> and intron 20 of <jats:italic>ALK.</jats:italic> © 2005 Wiley‐Liss, Inc.</jats:p>