title: Proximity of TPR and NTRK1 rearranging loci in human thyrocytes.
abstract: Chromosomal rearrangements are frequently associated with cancer; the mechanisms underlying their cell-type specificity are poorly understood. Papillary thyroid carcinomas are marked by a high frequency of chromosome rearrangements involving the RET and NTRK1 tyrosine kinase receptor genes and producing RET and TRK oncogenes. An explanation for the propensity of thyrocytes to undergo gene rearrangements has been recently proposed by Nikiforova and colleagues, who showed that the recombination between RET and H4 is favored by the loci proximity in interphase nuclei. We investigated whether the spatial proximity is a contributing factor also in the generation of the thyroid-specific TRK oncogenes. The distance between NTRK1 and its oncogenic partner TPR was determined by two-color fluorescence in situ hybridization and two-dimensional microscopy. A three-dimensional reconstruction of the data was also done. We show that the two loci in thyrocytes nuclei display a distance reduced with respect to peripheral blood lymphocytes, thus supporting the notion that spatial proximity of translocation-prone gene loci may favor gene rearrangements.
authors.affiliation: Department of Experimental Oncology Operative Unit Molecular Mechanisms of Cancer Growth and Progression, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Roccato
authors.forename: Paola
authors.initials: P
authors.lastname: Bressan
authors.forename: Guido
authors.initials: G
authors.lastname: Sabatella
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rumio
authors.forename: Laura
authors.initials: L
authors.lastname: Vizzotto
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: Angela
authors.initials: A
authors.lastname: Greco
mesh_terms: D002291:Carcinoma, Papillary / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000648:ultrastructure; D002478:Cells, Cultured; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D009857:Oncogenes / Q000235:genetics; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020917:Receptor, trkA / Q000235:genetics*; D013961:Thyroid Gland / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D013964:Thyroid Neoplasms / Q000235:genetics
chemical_list: D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C073597:TPR protein, human; D011505:Protein-Tyrosine Kinases; D020917:Receptor, trkA; C093573:ret-PTC fusion oncoproteins, human