New insights in the molecular signature of advanced medullary thyroid cancer: evidence of a bad outcome of cases with double RET mutations.
J Med Genet
; 53(11): 729-734, 2016 Nov.
Article
em En
| MEDLINE
| ID: mdl-27468888
ABSTRACT
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.
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Base de dados:
MEDLINE
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Revista:
J Med Genet
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Itália