has been identified in hereditary MEN2 syndrome, and is involved in sporadic medullary and papillary thyroid carcinoma (PTC) and Hirschsprung's disease (5).
(11-13) Further, reported molecular alterations involve the MET proto-oncogene (MET) and ret proto-oncogene
Healey et al., "Germ-line mutations of the RET proto-oncogene
in multiple endocrine neoplasia type 2 A," Nature, vol.
These 26 genes contained fibroblast growth factor receptor 1, G protein subunit alpha q, RB transcriptional corepressor 1, ABL proto-oncogene 1, B-Raf proto-oncogene, fibroblast growth factor receptor 3, guanine nucleotide-binding protein alpha stimulating ( GNAS ), HRas proto-oncogene ( HRAS ), fms-related tyrosine kinase 3, AKT serine/threonine kinase 1, ret proto-oncogene
, cadherin 1 ( CDH1 ), cyclin-dependent kinase inhibitor 2A, HER2 , enhancer of zeste 2 polycomb repressive complex 2 subunit, isocitrate dehydrogenase 1, isocitrate dehydrogenase 2, MET proto-oncogene, mutL homolog 1 ( MLH1 ), neuroblastoma RAS viral oncogene homolog ( NRAS ), catenin beta 1, janus kinase 2, NOTCH1 , protein tyrosine phosphatase nonreceptor type 11, janus kinase 3, and MPL proto-oncogene.
Elisei, "A comprehensive overview of the role of the RET proto-oncogene
in thyroid carcinoma," Nature Reviews.
The molecular alterations associated with PTC are BRAF mutations (50%), RET proto-oncogene
rearrangements RET/PTC (10-30%), RAS mutations (15%).
Other multiplexed digital PCR designs have recently permitted researchers, for instance, to simultaneously target ALK (anaplastic lymphoma receptor tyrosine kinase), ROS1 (ROS proto-oncogene 1, receptor tyrosine kinase), and RET (ret proto-oncogene
) fusions in lung cancer (24).
Hereditary syndromes of germline RET proto-oncogene
mutations are the cause of MTC in the remaining 25-30% of patients.
Takahashi, "cDNA cloning of mouse ret proto-oncogene
and its sequence similarity to the cadherin superfamily," Oncogene, vol.
In addition, future and ongoing clinical trials will not be limited to the targetable mutations described above and may involve mutations of other genes including ret proto-oncogene
(RET) and HER2/neu.
Caption: THYROID CANCER RET proto-oncogene
mutations increase risk.
Germline mutations in the RET proto-oncogene
cause hereditary MTC [20-22], and approximately 50% of patients with sporadic MTC have somatic RET mutations [23, 24].