title: A novel RET rearrangement (ACBD5/RET) by pericentric inversion, inv(10)(p12.1;q11.2), in papillary thyroid cancer from an atomic bomb survivor exposed to high-dose radiation.
abstract: During analysis of RET/PTC rearrangements in papillary thyroid cancer (PTC) among atomic bomb survivors, a cDNA fragment of a novel type of RET rearrangement was identified in a PTC patient exposed to a high radiation dose using the improved 5' RACE method. This gene resulted from the fusion of the 3' portion of RET containing tyrosine kinase domain to the 5' portion of the acyl-coenzyme A binding domain containing 5 (ACBD5) gene, by pericentric inversion inv(10)(p12.1;q11.2); expression of the fusion gene was confirmed by RT-PCR. ACBD5 gene is ubiquitously expressed in various human normal tissues including thyroid. Full-length cDNA of the ACBD5-RET gene was constructed and then examined for tumorigenicity. Enhanced phosphorylation of ERK proteins in the MAPK pathway was observed in NIH3T3 cells transfected with expression vector encoding the full-length ACBD5/RET cDNA, while this was not observed in the cells transfected with empty expression vector. Stable NIH3T3 transfectants with ACBD5-RET cDNA induced tumor formation after their injection into nude mice. These findings suggest that the ACBD5-RET rearrangement is causatively involved in the development of PTC.
authors.affiliation: Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan.
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Hamatani
authors.affiliation: Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Koyama
authors.affiliation: Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Mukai
authors.affiliation: Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Nakachi
authors.affiliation: Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kusunoki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D007446:Chromosome Inversion; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D041681:NIH 3T3 Cells; D009374:Neoplasms, Experimental; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D054043:Nuclear Weapons; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D011829:Radiation Dosage; D017741:Survivors; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C548478:ACBD5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human