RESUMO
Epithelial tumors of the thyroid are cytogenetically well-investigated tumors. So far, the main cytogenetic subgroups, characterized by trisomy 7 and by rearrangements of either 19q13 or 2p21, respectively, have been described. Recently, we have been able to describe the involvement of a novel gene called THADA in benign thyroid lesions with 2p21 rearrangements. Other fusion genes found in thyroid lesions are RET/PTC and PAX8/PPAR(gamma). The latter occurs in follicular thyroid carcinomas with a t(2;3)(q13;p25). Here we present molecular-cytogenetic and cytogenetic investigations on a follicular thyroid adenoma with a t(2;20;3)(p21;q11.2; p25). In this case, an intronic sequence of PPAR(gamma) is fused to exon 28 of THADA. We used BAC clones containing the genomic sequence of PPARgamma for fluorescence in situ hybridization to confirm the localization of the breakpoint within intron 2 of PPAR(gamma) . Our findings suggest that the close surrounding of PPAR(gamma) is a breakpoint hot spot region, leading to recurrent alterations of this gene in thyroid tumors of follicular origin including carcinomas as well as adenomas with or without involvement of PAX8.
Assuntos
Adenocarcinoma Folicular/genética , Quebra Cromossômica , Proteínas de Neoplasias/genética , PPAR gama/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/patologia , Processamento Alternativo , Mapeamento Cromossômico , Cromossomos Humanos Par 2 , Cromossomos Humanos Par 20 , Cromossomos Humanos Par 3 , Feminino , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/patologiaRESUMO
Structural rearrangements involving the long arm of chromosome 19 characterize a cytogenetic subgroup of benign thyroid tumors and constitute one of the most frequent specific chromosome abnormalities in epithelial tumors. Recently, we have been able to narrow down the breakpoint region affected in two cell lines to a region covered by a single PAC clone. Close to that region a candidate gene has been identified which we tentatively referred to as RITA (Rearranged In Thyroid Adenomas) now named ZNF331 according to HUGO nomenclature. However, the results had been obtained on two cell lines only making it necessary to extend the studies to a larger number of tumors including primary material. Herein, we have used four further primary tumors showing translocations involving 19q13 for fluorescence in situ hybridization (FISH) mapping studies using a variety of molecular probes from a 470-kbp cosmid/BAC contig. Ten new STSs were characterized and physically mapped within an EcoRI restriction map. The results enabled us to define an approximately 150-kbp breakpoint cluster region of the 19q13 aberrations in benign thyroid tumors flanked by two newly established STS markers.
Assuntos
Adenoma/genética , Quebra Cromossômica/genética , Cromossomos Humanos Par 19/genética , Mapeamento Físico do Cromossomo , Neoplasias da Glândula Tireoide/genética , Bandeamento Cromossômico , Fibroblastos , Humanos , Hibridização in Situ Fluorescente , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sitios de Sequências Rotuladas , Translocação Genética/genética , Células Tumorais CultivadasRESUMO
Rearrangements involving chromosome region 14q23-->q24 represent a main cytogenetic subgroup in a variety of benign solid tumors. Recently, in uterine leiomyomas containing the classical t(12;14)(q15;q23-->q24), the primary chromosome 14 target gene was identified as the protein kinase-encoding gene RAD51L1. In this report we show that RAD51L1 is also involved in the frequently occurring t(6;14) (p21;q23-->q24) in pulmonary chondroid hamartomas.
