RESUMEN
BACKGROUND.: An activating point mutation of the BRAF oncogene results in a V600E amino acid missense mutation found in a majority of papillary thyroid carcinomas (PTC). METHODS.: In this study, 28 matched tumor and serum samples obtained from patients with both benign and malignant thyroid disorders were analyzed for BRAF mutation using a gap-ligase chain reaction technique. RESULTS.: The BRAF mutation was absent in tumor DNA samples obtained from patients with benign adenomas, follicular neoplasms or carcinoma, and thyroid lymphoma. In contrast, 5 of 14 PTC tumors were positive for the BRAF mutation. Moreover, 3 of 14 patients with PTC were positive for BRAF mutation in serum and tumor. Of these 3 patients, 2 had lymph node metastasis and 2 had PTC in background of the Hashimoto's thyroiditis. CONCLUSIONS.: The detection of free circulating mutant BRAF in patients with PTC is possible and future studies are warranted to determine its clinical significance.
Asunto(s)
Carcinoma Papilar Folicular/genética , Carcinoma Papilar/genética , ADN de Neoplasias/genética , Proteínas Proto-Oncogénicas B-raf/sangre , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias de la Tiroides/genética , ADN de Neoplasias/sangre , Exones , Femenino , Enfermedad de Hashimoto , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la PolimerasaRESUMEN
In previous work, we showed that telomeres of normal cells are organized within the 3D space of the interphase nucleus in a nonoverlapping and cell cycle-dependent manner. This order is distorted in tumor cell nuclei where telomeres are found in close association forming aggregates of various numbers and sizes. Here we show that c-Myc overexpression induces telomeric aggregations in the interphase nucleus. Directly proportional to the duration of c-Myc deregulation, we observe three or five cycles of telomeric aggregate formation in interphase nuclei. These cycles reflect the onset and propagation of breakage-bridge-fusion cycles that are initiated by end-to-end telomeric fusions of chromosomes. Subsequent to initial chromosomal breakages, new fusions follow and the breakage-bridge-fusion cycles continue. During this time, nonreciprocal translocations are generated. c-Myc-dependent remodeling of the organization of telomeres thus precedes the onset of genomic instability and subsequently leads to chromosomal rearrangements. Our findings reveal that c-Myc possesses the ability to structurally modify chromosomes through telomeric fusions, thereby reorganizing the genetic information.