The RAS genes (HRAS, KRAS and NRAS) encode highly related G-proteins that play a central role in the intracellular transduction of signals arising from cell membrane receptors.
In its inactive state, RAS protein is bound to GDP. Upon activation, it releases GDP and binds GTP, thereby activating the MAPK and other signaling pathways, such as PI3K / AKT. Normally, the activated RAS-GTP protein becomes quickly inactive due to its intrinsic GTPase activity and the action of cytoplasmic GTPase-activating proteins.
Point mutations in the discrete domains of the RAS gene either increase its affinity for GTP (mutations in codons 12 and 13) or inactivate its autocatalytic GTPase function (mutation in codon 61). As a result, the mutant protein becomes permanently switched in the active position and continuously activates its downstream targets.
Point mutations involving several specific sites (codons 12, 13 and 61) of the NRAS, HRAS or KRAS genes are found in 10% to 20% of papillary thyroid carcinomas. Papillary thyroid carcinomas harboring RAS mutation almost always have follicular variant histology; this mutation also correlates with significantly less prominent nuclear features of papillary thyroid carcinoma, more frequent encapsulation and low rate of lymph node metastases.
Some studies have reported the association between RAS mutations and more aggressive behavior of papillary thyroid carcinoma, such as a higher frequency of distant metastases. Mutations of the RAS gene are not restricted to papillary thyroid carcinoma and also found in other benign and malignant thyroid neoplasms, as well as in tumors from other tissues.
The molecular pathogenesis of thyroid cancer involves dysregulation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K)/AKT pathways. Common activating mutations in the MAPK pathway include RET / PTC and NTRK rearrangements, and RAS and BRAF mutations. Common genetic alterations in the PI3K pathway include RAS mutations, PTEN mutations or deletions, PIK3K mutations or amplifications, and AKT1 mutations. PAX8 / PPARG fusions are common in FTC. Activation of Wnt/b-catenin pathway, inactivating mutations in TP53, and activating mutations in TERT promoter are frequent in undifferentiated thyroid cancer.#Arrangoiz #ThyroidSurgeon
My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida.
I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016.
Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida.
Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.
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Rodrigo Arrangoiz MS, MD, FACS, FSSO 