High Prevalence ofRASMutations inRET-Negative Sporadic Medullary Thyroid Carcinomas

Abstract

Overall, our results showed that RAS mutations were present in 68.0% (17 of 25) of the RET-negative MTC and in only 2.5% of the RET-positive MTC (P < 0.0001), suggesting that activation of the protooncogenes RAS and RET represents alternative genetic events in sporadic MTC tumorigenesis.

Częstość występowania mutacji somatycznych RAS w raku rdzeniastym tarczycy — analiza populacji polskiej

“…RAS mutation was detected in 26.5% of all sporadic MTC tumours, but when only RET-negative samples were considered, the prevalence of RAS mutation was 68.7%. A higher proportion of H-RAS mutation that constituted 72% of all detected RAS mutations was observed, which is consistent with all reported results [15,16,32] and comparable with studies published by Moura et al and Boichard et al that reported RAS mutations present in 68% and 81% of RET-negative sporadic MTC samples, respectively [14,16]. The results of different analyses of RAS mutations in MTC are controversial with reference to their different frequency reported by different studies.…”

“…It is associated with more aggressive course of the disease [11][12][13]. Recent studies suggest a high proportion of RAS somatic mutations in RET-negative tumours [14][15][16]. Thus, RAS gene mutations could be considered as an alternative genetic event in sporadic MTC tumorigenesis.…”

2813 Comprehensive genomic profiling of clinically advanced medullary thyroid carcinoma

“…The activating RET M918T mutation is the most frequent somatic and MEN2B germline alteration. Mutations in the RAS pathway have been identified in patients with RET wild-type sporadic MTC [29][30][31]. Retrospective nextgeneration sequencing studies of the exomes or select cancer genes in 17 and 20 sporadic MTC cases, respectively, confirmed mutant RET, HRAS, and KRAS as principal drivers.…”

Management of Rare Thyroid Malignancies

“…The remaining MTC is derived from an autosomal dominant hereditary pattern associated with the RET proto-oncogene. Hereditary MTC is more likely to be multifocal and bilateral in nature [53][54][55][56][57][58][59]. Thirty percent of MTC affects patients younger than 50 and can have a familial inheritance pattern including the association with multiple endocrine neoplasia (MEN) syndromes.…”