Genetic Landscape of Papillary Thyroid Carcinoma and Nuclear Architecture: An Overview Comparing Pediatric and Adult Populations.

Janete M Cerutti,Sabine Mai,Maria Isabel V Cordioli,Paola Caria,Luiza Sisdelli,Aline Rangel-Pozzo,Fernanda Vaisman

doi:10.3390/cancers12113146

Abstract

Simple SummaryPapillary thyroid carcinoma (PTC) represents 80–90% of all differentiated thyroid carcinomas. PTC has a high rate of gene fusions and mutations, which can influence clinical and biological behavior in both children and adults. In this review, we focus on the comparison between pediatric and adult PTC, highlighting genetic alterations, telomere-related genomic instability and changes in nuclear organization as novel biomarkers for thyroid cancers.Thyroid cancer is a rare malignancy in the pediatric population that is highly associated with disease aggressiveness and advanced disease stages when compared to adult population. The biological and molecular features underlying pediatric and adult thyroid cancer pathogenesis could be responsible for differences in the clinical presentation and prognosis. Despite this, the clinical assessment and treatments used in pediatric thyroid cancer are the same as those implemented for adults and specific personalized target treatments are not used in clinical practice. In this review, we focus on papillary thyroid carcinoma (PTC), which represents 80–90% of all differentiated thyroid carcinomas. PTC has a high rate of gene fusions and mutations, which can influence the histologic subtypes in both children and adults. This review also highlights telomere-related genomic instability and changes in nuclear organization as novel biomarkers for thyroid cancers.

Highlights

Thyroid carcinoma is the most common malignancy of the endocrine system in adult and pediatric populations
BRAFV600E has not been described in other follicular carcinomas or benign nodules, which suggests that this mutation is strongly associated with papillary thyroid carcinoma (PTC) [104,153]
We summarized the genetic landscape of adult and pediatric PTC, discussing post-Chernobyl and post-Fukushima pediatric cases

Summary

Introduction

Thyroid carcinoma is the most common malignancy of the endocrine system in adult and pediatric populations. In adults, this type of cancer is increasing dramatically in both men and women, with an average annual percentage change of 5.4% and 6.5%, respectively. Even though there is no indication of ethnic or race susceptibility in pediatric thyroid cancer, there has been a prevalence related to increasing age range, i.e., ages 5–9, 10–14, and 15–19 showing a prevalence of 10,000, 80,000, and 310,000, respectively [19]. PTC is further subdivided based on histological variants, such as the classic (CVPTC), follicular (FVPTC), solid (SVPTC), and diffuse sclerosing (DSVPTC) variants Among these variants, children under the age of 10 seem to be unaffected by the most common type, CVPTC, found in adults [26]. We will discuss aspects of the PTC histotype in adults and children, with a focus on differences in genetic alterations, telomere-related genomic instability, and nuclear architecture

Epidemiology and Pathogenesis

Epidemiologic

Molecular Features

BRAF Alterations

ETV6-NTRK3 Rearrangement

STRN-ALK Rearrangement

PAX8-PPARγ Rearrangement

RAS Mutations

Telomere-Related Genomic Instability and Nuclear Architecture

Conclusions and Future

Findings

Conclusions and Future Perspectives