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Do Molecular Profiles of Primary Versus Metastatic Radioiodine Refractory Differentiated Thyroid Cancer Differ?

Authors :
Athanasios Bikas
Vasily Vasko
Kirk Jensen
Sarika N. Rao
Cristiane Gomes-Lima
Luiz Claudio Castro
Matthew McCoy
Rebecca Feldman
Jacqueline Jonklaas
Kenneth D. Burman
Leonard Wartofsky
Leila Shobab
Wen Lee
Di Wu
Dorina Ylli
Source :
Frontiers in Endocrinology, Vol 12 (2021)
Publication Year :
2021
Publisher :
Frontiers Media SA, 2021.

Abstract

Management of metastatic radioiodine refractory differentiated thyroid cancer (DTC) can be a therapeutic challenge. Generally, little is known about the paired molecular profile of the primary tumor and the metastases and whether they harbor the same genetic abnormalities. The present study compared the molecular profile of paired tumor specimens (primary tumor/metastatic sites) from patients with radioiodine refractory DTC in order to gain insight into a possible basis for resistance to radioiodine. Twelve patients with radioiodine refractory metastases were studied; median age at diagnosis of 61 years (range, 25–82). Nine patients had papillary TC (PTC), one had follicular TC (FTC), and two had Hürthle cell TC (HTC). Distant metastases were present in the lungs (n = 10), bones (n = 4), and liver (n = 1). The molecular profiling of paired tumors was performed with a panel of 592 genes for Next Generation Sequencing, RNA-sequencing, and immunohistochemistry. Digital microfluidic PCR was used to investigateTERTpromoter mutations. The genetic landscape of all paired sites comprisedBRAF,NRAS,HRAS,TP53,ATM,MUTYH,POLE, andNTRKgenes, includingBRAFandNTRKfusions.BRAFV600E was the most common point mutation in the paired specimens (5/12).TERTpromoter mutation C228T was detected in one case. PD-L1 expression at metastatic sites was highly positive (95%) for one patient with HTC. All specimens were stable for microsatellite instability testing, and the tumor mutation burden was low to intermediate. Therefore, the molecular profile of DTC primary and metastatic lesions can show heterogeneity, which may help explain some altered responses to therapeutic intervention.

Details

ISSN :
16642392
Volume :
12
Database :
OpenAIRE
Journal :
Frontiers in Endocrinology
Accession number :
edsair.doi.dedup.....88e8d30aa0d28e19245f5de21651059e
Full Text :
https://doi.org/10.3389/fendo.2021.623182