New insights in the molecular signature of advanced medullary thyroid cancer: evidence of a bad outcome of cases with doubleRETmutations
| العنوان: | New insights in the molecular signature of advanced medullary thyroid cancer: evidence of a bad outcome of cases with doubleRETmutations |
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| المؤلفون: | Laura Valerio, Raffaele Ciampi, Valeria Bottici, Clara Ugolini, Fulvio Basolo, Alessia Tacito, Liborio Torregrossa, Francesca Casella, David Viola, Antonio Matrone, Virginia Cappagli, Paolo Vitti, Cristina Romei, Paolo Piaggi, Rossella Elisei, Gabriele Materazzi |
| المصدر: | Journal of Medical Genetics. 53:729-734 |
| بيانات النشر: | BMJ, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | congenital, hereditary, and neonatal diseases and abnormalities, endocrine system, medicine.medical_specialty, endocrine system diseases, Somatic cell, 030209 endocrinology & metabolism, medullary thyroid cancer, Thyroid carcinoma, Pathogenesis, 03 medical and health sciences, Exon, 0302 clinical medicine, Germline mutation, Molecular genetics, Genetics, medicine, ret, neoplasms, ras, Genetics (clinical), Cancer: endocrine, Oncogene, business.industry, Medullary thyroid cancer, medicine.disease, 030220 oncology & carcinogenesis, Cancer research, business |
| الوصف: | Background The RET proto-oncogene is responsible for the pathogenesis of hereditary (98%) and sporadic (40%) medullary thyroid carcinoma (MTC). In sporadic MTC, somatic RET mutations are associated with a poor prognosis. Objectives We looked at the genetic profile of patients with advanced and metastatic MTC. The correlation between these mutations and outcome was also investigated. Methods 70 patients with advanced and metastatic sporadic MTC were studied. Exons 10-11 and 13-16 of RET were analysed by direct sequencing. All cases were studied for RAS and the majority also for TERT mutations. RET/RAS-negative cases were analysed for other oncogene mutations. Results 64/70 cases (91.4%) showed a somatic mutation, while 6 (8.6%) were negative. Among the mutated cases, RET mutations, mainly M918T, were the most prevalent (93.8%). K- or H-RAS mutations were present in 6.2% of cases and were mutually exclusive with RET. No other mutations were found. Four tumours showed two RET somatic mutations. We found a complex somatic RET alteration in 6/60 (10%) RET-positive sporadic MTC cases. A positive correlation between a poor prognosis and the multiple number of RET mutations was found. Conclusions This study showed a high prevalence of somatic RET mutations in advanced and metastatic MTCs. RAS mutations were present in a small percentage of cases and mutually exclusive with RET mutations. In a small number of cases, more than one RET mutation was present in the same tissue. RET double mutations and, to a lesser extent, also complex mutations showed a worse outcome. |
| تدمد: | 1468-6244 0022-2593 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::44e2b283767974fc70a20ef98624f563Test https://doi.org/10.1136/jmedgenet-2016-103833Test |
| رقم الانضمام: | edsair.doi.dedup.....44e2b283767974fc70a20ef98624f563 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14686244 00222593 |
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