title: Identification of novel ALK rearrangement A2M-ALK in a neonate with fetal lung interstitial tumor.
abstract: Fetal lung interstitial tumor (FLIT) is a recently reported type of congenital lung lesion comprising solid and cystic components. The pathological features include unique interstitial mesenchyme-based cell proliferation, and differ from other neoplasms represented by pleuropulmonary blastoma or congenital peribronchial myofibroblastic tumor. FLIT is extremely rare and its gene expression profile has not yet been reported. We provide the first report of a novel chromosomal rearrangement resulting in α-2-macroglobulin (A2M) and anaplastic lymphoma kinase (ALK) gene fusion in a patient with FLIT. The tumor cells contained a t(2;12)(p23;p13) and were mesenchymal in origin (e.g., inflammatory myofibroblastic tumors), suggesting the involvement of ALK in this case of FLIT. Break apart fluorescence in situ hybridization demonstrated chromosomal rearrangement at ALK 2p23. Using 5'-rapid amplification of cDNA ends, we further identified a novel transcript fusing exon 22 of A2M to exon 19 of ALK, which was confirmed by reverse-transcription polymerase chain reaction. The corresponding chimeric gene was subsequently confirmed by sequencing, including the genomic break point between intron 22 and 18 of A2M and ALK, respectively. Discovery of A2M as a novel ALK fusion partner, together with the involvement of ALK, provides new insights into the pathogenesis of FLIT, and suggests the potential for new therapeutic strategies based on ALK inhibitors.
authors: Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan; Department of Immunology, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors: Tadashi
authors: T
authors: Onoda
authors: Miyako
authors: M
authors: Kanno
authors: Hiroko
authors: H
authors: Sato
authors: Noriyuki
authors: N
authors: Takahashi
authors: Hiroko
authors: H
authors: Izumino
authors: Hiroshi
authors: H
authors: Ohta
authors: Takaki
authors: T
authors: Emura
authors: Hirohisa
authors: H
authors: Katoh
authors: Hiroyuki
authors: H
authors: Ohizumi
authors: Hiroya
authors: H
authors: Ohtake
authors: Hironobu
authors: H
authors: Asao
authors: Louis P
authors: LP
authors: Dehner
authors: Ashley D
authors: AD
authors: Hill
authors: Kiyoshi
authors: K
authors: Hayasaka
authors: Tetsuo
authors: T
authors: Mitsui
mesh_terms: D002889:Chromosomes, Human, Pair 2; D005091:Exons; D006801:Humans; D007231:Infant, Newborn; D007621:Karyotyping / Q000379:methods; D008175:Lung Neoplasms / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D000511:alpha-Macroglobulins / Q000235:genetics*
chemical_list: D015514:Oncogene Proteins, Fusion; D000511:alpha-Macroglobulins; C000596162:A2M-ALK fusion protein, human; D020794:Receptor Protein-Tyrosine Kinases