Background: The prevalence of thyroid cancer survivors is rising rapidly due to the combination of an increasing incidence, high survival rates, and a young age at diagnosis. The physical and psychosocial morbidity of thyroid cancer has not been adequately described, and this study therefore sought to improve the understanding of the impact of thyroid cancer on quality of life (QoL) by conducting a large-scale survivorship study. Methods: Thyroid cancer survivors were recruited from a multicenter collaborative network of clinics, national survivorship groups, and social media. Study participants completed a validated QoL assessment tool that measures four morbidity domains: physical, psychological, social, and spiritual effects. Data were also collected on participant demographics, medical comorbidities, tumor characteristics, and treatment modalities. Results: A total of 1174 participants with thyroid cancer were recruited. Of these, 89.9% were female, with an average age of 48 years, and a mean time from diagnosis of five years. The mean overall QoL was 5.56/10, with 0 being the worst. Scores for each of the sub-domains were 5.83 for physical, 5.03 for psychological, 6.48 for social, and 5.16 for spiritual well-being. QoL scores begin to improve five years after diagnosis. Female sex, young age at diagnosis, and lower educational attainment were highly predictive of decreased QoL. Conclusion: Thyroid cancer diagnosis and treatment can result in a decreased QoL. The present findings indicate that better tools to measure and improve thyroid cancer survivor QoL are needed. The authors plan to follow-up on these findings in the near future, as enrollment and data collection are ongoing.

Transcription by RNA polymerase II is antagonized by the presence of a nearby tRNA gene in Saccharomyces cerevisiae. To test hypotheses concerning the mechanism of this tRNA gene-mediated (tgm) silencing, the effects of specific gene deletions were determined. The results show that the mechanism of silencing near tRNA genes is fundamentally different from other forms of transcriptional silencing in yeast. Rather, tgm silencing is dependent on the ability to cluster the dispersed tRNA genes in or near the nucleolus, constituting a form of three-dimensional gene control.Chromatin-mediated transcriptional silencing has been extensively studied in Saccharomyces cerevisiae: at the two silent mating type loci, near telomeres, and in the single cluster of tandemly repeated rRNA genes (1). Mutations affecting these silencing forms affect chromatin structure by altering histone modifications and remodeling. Unlike other eukaryotes, S. cerevisiae appears to lack RNA-mediated forms of silencing (2).Actively transcribed tRNA genes can suppress transcription of nearby genes by RNA polymerase II (pol II) 1 in yeast (3,4). This phenomenon, termed either tRNA gene position effect (5) or tRNA gene-mediated (tgm) silencing (6), is independent of the tRNA gene orientation and does not involve simple steric blockage of RNA pol II upstream activator sites (6). It is dependent on transcription of the tRNA gene, since mutations in the pol III promoters and conditional mutations in RNA polymerase III (pol III) alleviate tgm silencing. The degree to which this effect suppresses nearby pol II transcription varies depending the pol II promoter (6).Unlike other silencing elements, tRNA genes are scattered throughout the genome in large numbers and could potentially influence neighboring genes, although pol II promoters are underrepresented near tRNA genes (5). Notable exceptions to this are the Ty retrotransposons (5,7,8), which appear to have adapted to the environment and preferentially insert near tRNA genes. The mechanism of tgm silencing is unknown, but genetic and cytological data suggest that it might be linked to spatial organization of the tRNA genes in the nucleus. The early pre-tRNA processing pathway and most tRNA genes associate with the nucleolus in yeast (9, 10), and tgm silencing is released by a mutation affecting nucleolar rRNA processing (6).To explore the mechanism of tgm silencing we have examined its relationship to other silencing forms and its dependence on nucleolar localization. MATERIALS AND METHODSYeast Strains and Genetic Manipulations-The strains used for screening gene deletions is BY4741 (MATa his3⌬1 leu2⌬0 met15⌬0 ura3⌬0 GAL4 GAL80) and its derivatives, ResGen Invitrogen Corp. (Carlsbad, CA). Deletions affecting tgm silencing were confirmed by PCR. Growth on selective media was performed by standard methods except that the G418 concentration in kanamycin selections was doubled (11).Identification of Silencing Suppressors-The deleted gene strains with plasmid pSUP4o (4) were plated on four different syntheti...