title: Heterogeneity in the distribution of RET/PTC rearrangements within individual post-Chernobyl papillary thyroid carcinomas.
abstract: The nuclear disaster that occurred in Chernobyl in 1986 offered the unique opportunity to study the molecular genetics of one human tumor type, papillary carcinoma of the thyroid gland, associated with a specific etiology. We have analyzed RET rearrangements in post-Chernobyl papillary thyroid carcinomas (n = 29), follicular thyroid adenomas (n = 2), and follicular thyroid carcinoma (n = 1) by interphase fluorescence in situ hybridization (FISH) analysis on paraffin-embedded tissue sections. Paraffin sections were microdissected before use to ensure that only tumor was present. Cell nuclei were scored for the presence of a split FISH signal (separated red and green signal) in addition to an overlapping signal. Only cells with either two overlapping signals or one split and one overlapping signal were counted to ensure that only complete cell nuclei had been scored. In total, 23 of 32 cases (72%) showed RET rearrangements diagnosed by FISH interphase analysis. In all cases, the tumors were composed of a mixture of cells with and without ret rearrangement on FISH. In some cases, this distribution was clearly nonrandom because clustering of rearranged cells was detected within the same tumor nodule. Accordingly, only 31% of the cases positive for rearrangement on FISH also scored positive using RT-PCR. These findings suggest that because RET/PTC rearrangements are not present in a majority of tumor cells, either a fraction of post-Chernobyl papillary thyroid tumors are of multiclonal origin, or ret rearrangement is a later, subclonal event.
authors.affiliation: GSF-Forschungszentrum für Umwelt und Gesundheit GmbH, Institute of Molecular Radiobiology, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany.
authors.forename: Kristian
authors.initials: K
authors.lastname: Unger
authors.forename: Horst
authors.initials: H
authors.lastname: Zitzelsberger
authors.forename: Giuliana
authors.initials: G
authors.lastname: Salvatore
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
authors.forename: Tatjana
authors.initials: T
authors.lastname: Bogdanova
authors.forename: Herbert
authors.initials: H
authors.lastname: Braselmann
authors.forename: Peter
authors.initials: P
authors.lastname: Kastner
authors.forename: Lyudmilla
authors.initials: L
authors.lastname: Zurnadzhy
authors.forename: Nikolay
authors.initials: N
authors.lastname: Tronko
authors.forename: Peter
authors.initials: P
authors.lastname: Hutzler
authors.forename: Gerry
authors.initials: G
authors.lastname: Thomas
mesh_terms: D000293:Adolescent; D002291:Carcinoma, Papillary / Q000235:genetics*; D002648:Child; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011210:Power Plants; D051096:Proto-Oncogene Proteins c-ret; D018788:Radioactive Hazard Release; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics*; D014455:Ukraine
chemical_list: D015513:Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases