Childhood Thyroid Carcinoma: Molecular Characterization and Investigation of C1ORF24, ITM1 and PVALB Gene Expression

Abstract

Thyroid neoplasms are the most frequent endocrine tumors in adults. Althought rare, children´s thyroid tumors represent 1-2% of pediatrics tumors and compared to adults, childhood tumors are usually bilateral, multifocals, present capsule invasion and lymphnode metastasis at diagnosis and 10-20% have distant metastasis. However, tumors in children have an excellent prognostic. Children and teenagers usually present papillary thyroid carcinoma (72%), and follicular and diffuse sclerosing variants are the most common. Medullar thyroid carcinoma represents 5% of pediatric tumors and it´s usually associated to hereditary syndrome characterized by multiple endrocrine neoplasia syndrome type 2 (MEN2).Among thyroid tumors in adults, papillary carcinomas are best characterized. Genetic alterations in MAPK (Map kinase) pathway, such as rearrangements RET / PTC or BRAF and RAS point mutations occur in approximately 75% of cases. Between then, BRAF mutation (p.Val600Glu) is the most prevalent and has been correlated with more aggressive tumors, extrathyroid extension, tumor recurrence, lymph node metastasis and distant metastasis. In addition, the mutation p.Val600Glu has been associated with decreased expression of genes related to iodine metabolism, such as NIS, TG, TPO and TSH-R. Follicular carcinoma has been associated with the presence of PAX8-PPAR³ rearrangement, and mutations in RAS family genes. However, these alterations do not allow the differential diagnosis between benign adenomas and follicular carcinoma because of low sensitivity and specificity.On the other hand, little is known about the genetic events associated with pediatrics tumor´s pathogenesis and expression levels of genes associated with iodine metabolism. The identification of genetic alterations and / or signaling pathways associated with the apperaring of thyroid cancer in pediatric patients is extremely important not only for understanding the mechanisms associated with the pathogenesis, but also in the diagnosis, treatment and prognosis of thyroid tumors in children.Thus, initially, the aim of this study is to investigate the prevalence of RET/PTC rearrangements, commonly identified in adults, in a series of pediatric patients. Still, correlate these results with NIS, TG, TPO and TSH-R gene expression and clinical and pathological features. Later, we will investigate the expression of ITM1, C1orf24 and PVALB, whose expression can distinguish malignant from benign nodules in adults with high sensitivity and specificity.