Copy Number Alterations in Papillary Thyroid Carcinomas: Does Loss of SESN2 Have a Role in Age-related Different Prognoses?

Abstract

Thyroid cancer is the only tumor in which age is an important prognostic factor. In papillary thyroid carcinomas (PTC), 45 years of age seems to be a key point that divides adult patients into two groups, with different clinical features. The aim of the study was to perform a microarray-based analysis in two groups of patients (<45 and ≥45 years old), in order to verify the occurrence of specific copy number alterations (CNAs) that could be associated to different patient behaviors associated with age. In order to search and compare genomic alterations that may be related to age, we evaluated the occurrence of CNAs in the genome of 24 PTC samples, divided in two groups (<45 and ≥45 years old). We identified only one region showing a statistically significant difference between the groups (p=0.00357): a deletion of approximately 537 kps in 1p35.3., which was more frequent in patients aged 45 years or older. This is the region where, among others, the gene SESN2 is located, which is activated under oxidative stress and plays an antioxidant role, in addition to protecting the genetic material from damage generated by reactive oxygen species (ROS). This is the first time that a CNA involving the deletion of the SESN2 gene is associated with papillary thyroid carcinomas, particularly in patients aged 45 years and older, indicating that this deletion would lead to a more malignant and prominent tumoral behavior associated to a worst prognosis.