Furthermore, activation of specific subtypes of the ret/PTC tyrosine kinase oncogene appears to be more common in radiation-associated thyroid cancers than in spontaneous thyroid cancers.
Point mutations of the RET receptor tyrosine kinase are responsible for the inheritance of multiple endocrine neoplasia (MEN) type 2 syndromes and are also present in a fraction of sporadic medullary thyroid carcinomas.
We report the finding of a novel missense mutation at codon 833 in the tyrosine kinase of the RET proto-oncogene in a patient with a carcinoma of the thyroid.
The catalytic domain of RET can be used also for X-ray diffraction to obtain information about the three-dimensional structure, necessary for a rational design of selective inhibitors: it represents an important tool to understand the molecular mechanisms causing thyroid cancer and to care it.
Mutations of the RET protooncogene (a growth factor receptor) occur in nearly all familial medullary thyroid carcinomas and may be used for family screening.
We evaluated the best tagging SNPs from our previous PTC study and additionally included SNPs in or near FOXE1 and NKX2-1 genes, known susceptibility loci for thyroid cancer.
This study demonstrates that all thyroid carcinomas harboring activating RET rearrangements exhibit a well-differentiated phenotype, that of papillary carcinoma, and indicates that the subset of RET/PTC-positive papillary carcinomas do not progress to more aggressive, less differentiated tumor phenotypes.
In contrast, the significance of somatic RET mutations in sporadic MTC is unknown. p53 seems to play a crucial role in the dedifferentiation process of thyroid carcinoma.
Although the mechanisms of cellular injury and repair resulting from ionizing radiation are well described, the genomics of radiation-induced tumours are still relatively poorly understood, with some exceptions, such as RET rearrangement in thyroid carcinomas following iodine-131 exposure and MYC amplification in cutaneous angiosarcoma following chest wall irradiation for breast cancer.
Somatic mutations in RET exons 12 and 15 in sporadic medullary thyroid carcinomas: different spectrum of mutations in sporadic type from hereditary type.
In few papillary thyroid carcinomas (PTC) and oxyphilic thyroid carcinoma, the clinical impact of the 15 known RET hybrid oncogene variants (RET/PTC 1 to 12, 1L, 3r2, 3r3) is subject to controversial discussions.
Because RET/PTC rearrangements are unique to thyroid carcinomas, our findings support the clinical evaluation of sorafenib for patients with PTC and the identification of patients most likely to respond to sorafenib treatment.