Assessment of three germline RET variants

Multiple endocrine neoplasia type 2 (MEN2) and apparently sporadic medullary thyroid carcinoma (AS-MTC) are caused by inherited activating mutations of the RET proto-oncogene. Following screening for RET mutations in patients, rare mutations have been found and these variants require study to assess their pathogenic potential. Prazeres and colleagues assessed the function of three previously uncharacterised germline RET variants. The variants Arg886Trp and Glu511Lys had increased in vitro transforming potential, showing higher numbers of foci relative to wild type RET in NIH3T3 focus formation assays, and higher numbers of colonies in soft-agar assays. However, Cys634Arg, a high-risk level 2 mutation, had a higher transforming efficiency. The effects of sorafenib, a kinase inhibitor, were also assessed: the transforming activity of RET variants was inhibited by sorafenib, highlighting sorafenib treatment as a potential therapeutic option. Prazeres et al. (2011) Endocrine-Related Cancer 18 401-412.

Read the full article at: DOI:10.1530/ERC-10-0258.