Furthermore, when we compared MTC outcome according to different RET mutations (M918T
cases versus non-M918T ones), we found a significant association between the presence of the M918T
mutation and persistent disease (p = 0.02, by chi-squared test).
We also examined the effect of lenvatinib on the phosphorylation of RET with the M918T
The majority of MEN2A and FMTC cases involve mutations in the Cys-rich domains of exons 10 and 11, whereas 98% of patients with MEN213 have a transition involving codon 918 (ATG[right arrow]ACG) in exon 16 of the RET protooncogene (M918T
) (30) (Fig.
In most clinical laboratories, the direct sequencing of exons containing hotspots of the RET protooncogene is routinely performed in all MTC patients (except for cases in which MEN 2B is suspected, where a direct analysis of the M918T
mutation is the first step of the molecular evaluation).
As stated, although the common MEN 2B mutation in exon 16 (M918T
) removes a Fok I site and could therefore be easily analyzed by restriction digest, exons 10 and 11 harbor a variety of mutations in multiple codons in MEN 2A and MTC patients (see Table 1 in reference 11).