RESUMO
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.
Assuntos
Neoplasias Pulmonares/genética , Proteínas de Fusão Oncogênica/genética , Receptores Proteína Tirosina Quinases/genética , alfa-Macroglobulinas/genética , Cromossomos Humanos Par 2 , Éxons , Humanos , Recém-Nascido , Cariotipagem/métodos , Neoplasias Pulmonares/congênito , Neoplasias Pulmonares/patologia , MasculinoRESUMO
Primary leiomyosarcoma of the respiratory tract is a very rare malignancy, especially in childhood, with only 15 cases in patients under 16 years old having been reported. In the present case, the survival period from the onset of symptoms has been over 7 years, despite incomplete resection. Based on the 15 published cases, the prognosis is poorer when the tumor is unresected or incompletely resected, but under favorable circumstances, prolonged survival is possible.
