WCMC logo
PMKB
  • WCMC logoPMKB
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity
  • Login
RET
  • Information
  • View History
  • Pending Review
Interpretation 2155
Tier 1
RET
Variants
RET M918T
Primary Sites
Thyroid
Tumor Types
Medullary Carcinoma
Interpretation

Proto-oncogene tyrosine-protein kinase receptor RET, activates the MAPK pathway for cell proliferation and the PI3K/AKT pathway for cell survival. RET activating mutations and rearrangements are common in medullary thyroid carcinomas. 25-30% of medullary thyroid carcinomas are associated with germline RET mutations. In these germline mutations, the most commonly affected codons are 609, 611, 618, 620 (exon 10) and 634 (exon 11), encoding for the extracellular cysteine-rich domain, and codons 768 (exon 13) and 804 (exon 14) of the intracellular tyrosine kinase domain. Sporadic RET mutations have been reported in 61.5% of medullary thyroid carcinomas. In sporadic cases, the M918T mutation is most commonly reported and may indicate a poor prognosis. Given these identified molecular alterations, therapies targeting the RET signaling pathway have been used and shown to provide advantages over traditional cytotoxic therapy with regard to disease response. There are multiple ongoing clinical trials on cabozantinib (tyrosine kinase inhibitor), sorafenib (multikinase inhibitor), and everolimus (mTOR inhibitor).

Citations
  1. Figlioli G, et al. Medullary thyroid carcinoma (MTC) and RET proto-oncogene: mutation spectrum in the familial cases and a meta-analysis of studies on the sporadic form. Mutat Res. 2013 Jan-Mar;752(1):36-44.
  2. Pusztaszeri MP, Bongiovanni M, Faquin WC. Update on the cytologic and molecular features of medullary thyroid carcinoma. Adv Anat Pathol. 2014 Jan;21(1):26-35.
  3. Hassan B, et al. Catalytic mTOR inhibitors can overcome intrinsic and acquired resistance to allosteric mTOR inhibitors. Oncotarget. 2014 Sep 30;5(18):8544-57.
  4. Hong D, et al. Medullary thyroid cancer: targeting the RET kinase pathway with sorafenib/tipifarnib. Mol Cancer Ther. 2008 May;7(5):1001-6.
  5. Wilhelm SM, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases
  6. involved in tumor progression and angiogenesis. Cancer Res. 2004 Oct 1;64(19):7099-109.
  7. Yakes FM, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011 Dec;10(12):2298-308.
Last updated: 2018-04-05 01:42:13 UTC
PMKB Bot
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity

Disclaimer: You assume full responsibility for all risks associated with using this PMKB website. The Englander Institute for Precision Medicine at Weill Cornell Medicine makes no guarantee of the comprehensiveness, reliability or accuracy of the information on this website and assumes no responsibility for errors in the information associated with this web site. Healthcare providers and patients must integrate all clinical and laboratory findings as well as information from a variety of sources before deciding on appropriate clinical care options.


When using PMKB, please cite: Huang et al., JAMIA 2017


HELP
User Guide
Video Tutorial
INFO
About
Latest
API
Twitter
CONTACT US
Contact

Englander Institute for Precision Medicine
© Weill Cornell Medicine | Version 1.7.2Privacy PolicyTerms of use