RESUMEN
A high prevalence of the activating BRAF mutation, BRAF(T1796A), is observed in adult papillary thyroid carcinomas (PTCs). The prognosis of childhood PTCs is generally fairly good despite the fact that distant metastases are often documented in these cases. To investigate the differences between the characteristics of childhood and adult PTCs, we analyzed both BRAF(T1796A) and RAS mutations in 31 Japanese and 48 post-Chernobyl Ukrainian thyroid carcinomas. In the 31 Japanese childhood cases, BRAF(T1796A) was found in only one instance (3.2%), and no RAS mutations were detected. In the Ukrainian subjects, of the 15 childhood and the 33 adolescent and young adult PTCs examined, the BRAF(T1796A) mutation was found in zero and eight cases, respectively, and RAS mutations were found in two of the young adult cases. In addition, 17 of the 48 Ukrainian cases showed expression of the RET tyrosine kinase region, indicating the existence of RET/PTC rearrangements. Unlike adult PTCs, we could detect no positive association between BRAF(T1796A) mutations and clinical parameters in the childhood carcinomas, suggesting that a low prevalence of BRAF(T1796A) is a common feature of PTCs in children regardless of radiation exposure levels. The differences in the prevalence of BRAF(T1796A) mutations between childhood and adult cases of PTC may well reflect inherent differences in the clinical features of these cancers between the two age groups.
Asunto(s)
Mutación , Proteínas Proto-Oncogénicas c-raf/genética , Neoplasias de la Tiroides/genética , Adolescente , Carcinoma Papilar/genética , Niño , Preescolar , Femenino , Reordenamiento Génico , Humanos , Lactante , Masculino , Proteínas Oncogénicas/genética , Centrales Eléctricas , Proteínas Proto-Oncogénicas B-raf , Proteínas Proto-Oncogénicas c-ret , Liberación de Radiactividad Peligrosa , Proteínas Tirosina Quinasas Receptoras/genética , UcraniaRESUMEN
Point mutations of the BRAF gene have been recently described with high prevalence in papillary thyroid carcinomas. However, this molecular alteration has not been studied in radiation-induced thyroid tumors. We analyzed the prevalence of BRAF point mutations and RET/PTC rearrangements in 55 post-Chernobyl papillary carcinomas, compared with 82 sporadic papillary carcinomas. Radiation-induced tumors demonstrated a low prevalence (4%) of BRAF point mutations and high prevalence (58%) of RET/PTC rearrangements. Sporadic papillary carcinomas revealed a clearly distinct pattern, with 37% of tumors harboring BRAF mutations and 20% RET/PTC rearrangements. These results demonstrate a significant difference in the molecular genetic profile of sporadic and radiation-induced thyroid tumors.