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Authors
Abstract(s)
Thyroid cancer is the most frequente endocrine neoplasm, being the tenth most prevalente in both genders and presents na overall good prognosis. Ras related 2 (RRas2), also known as TC21, is a GTP-binding protein that together with RRas1 and RRas3, is parto f the RRas GTPase subfamily. Mutations in RRas2 gene in the long-tailed hotspot Q72L/H block the hydrolysis of guanosine trophosphate (GTP) in Ras superfamily proteins, generating constitutively active proteins that will preferentially bound to GTP. In mice models, the insertion of the mutation RRas2 Q72L/H is associated to the ocurrence of thyroid tumours. This gen is composed by five exons encoding a member of the Ras superfamily that participates in the RAS-MAPK pathway. The ACD gene, also known as TPP1, encodes the telomere-binding protein TPP1 which recruits telomerase to telomeres. When adressing the promoter of this gene, we refer to it as the TPP1 promoter (TPP1p). TPP1 protein plays a key role in the telomere stability and lenght regulation. Mutations in its promoter were reported to create novel transcription factor binding sites as previously presented for telomerase promoter (TERTp). Co-expression of these two genes lead to telomere elongation, indicating that mutations in the TPP1 and TERTp can cooperate for the immortalisation of cancer cells. Our project aimed to evaluate mutations in the Q72L hotspot of the RRAS2 gene and in the TPP1p in thyroid tumours. Following genotyping of RRas2, we conclude that the presence of mutations in the Q72L hotspot may not represente a frequente oncogenic event, as we did not detect them. For TPP1p, although already presented in the literature, these alterations were not detected in our series, suggesting that they may be a rare event in thyroid tumours.
Description
Keywords
Thyroid cancer RRaS2gene Q72L/Hhotspot Telomerase promotor (TERTp) TPP1 promotor (TPP1p)