title: Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor.
abstract: 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 ALK gene, serving as the 3'-partner in fusion genes with various translocation partners. In the present study, we describe the finding of a novel SEC31L1/ALK fusion gene in an intraabdominal IMT of a young man. G-band analysis revealed a translocation t(2;4)(p23;q21) and subsequent fluorescence in situ hybridization with locus-specific probes strongly indicated disruption of the ALK locus on chromosome 2. Immunostaining with monoclonal mouse anti-human CD246 ALK Protein showed diffuse cytoplasmic positivity. Using reverse primers for the ALK-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 SEC31L1 (NM_016211), located in band 4q21, was fused in-frame to nt 4080 of ALK (NM_004304). RT-PCR with two sets of primer pairs specific for SEC31L1 and ALK amplified two transcripts, which at sequencing corresponded to two types of chimeric SEC31L1/ALK transcripts. In the long, type I, transcript nt 3012 of SEC31L1 (NM_016211) was fused in-frame to nt 4080 of ALK. In the short, type II, transcript nt 2670 of SEC31L1 was fused in-frame to nt 4080 of ALK. Genomic PCR and subsequent sequencing showed that the breakpoints were located in intron 23 of SEC31L1 and intron 20 of ALK.
authors.affiliation: Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden. ioannis.panagopoulos@med.lu.se
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
authors.forename: Therese
authors.initials: T
authors.lastname: Nilsson
authors.forename: Henryk A
authors.initials: HA
authors.lastname: Domanski
authors.forename: Margareth
authors.initials: M
authors.lastname: Isaksson
authors.forename: Pia
authors.initials: P
authors.lastname: Lindblom
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
mesh_terms: D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D007621:Karyotyping; D008297:Male; D008969:Molecular Sequence Data; D009379:Neoplasms, Muscle Tissue / Q000235:genetics* / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; C507455:SEC31A protein, human; D033921:Vesicular Transport Proteins; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases